NO343067B1 - DPP IV-hemmerformuleringer, fremgangsmåte for fremstilling av slike samt doseformer inneholdende slike - Google Patents
DPP IV-hemmerformuleringer, fremgangsmåte for fremstilling av slike samt doseformer inneholdende slike Download PDFInfo
- Publication number
- NO343067B1 NO343067B1 NO20084256A NO20084256A NO343067B1 NO 343067 B1 NO343067 B1 NO 343067B1 NO 20084256 A NO20084256 A NO 20084256A NO 20084256 A NO20084256 A NO 20084256A NO 343067 B1 NO343067 B1 NO 343067B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- xanthine
- butyn
- amino
- pharmaceutical preparation
- Prior art date
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Classifications
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Abstract
Foreliggende oppfinnelse angår farmasøytiske preparater av DPP IV-hemmere med en aminogruppe, fremstilling av dem og anvendelse av dem for å behandle diabetes mellitus.
Description
Foreliggende oppfinnelse angår farmasøytiske preparater av valgte DPP IV-hemmere, fremstilling av dem og anvendelse av dem for å behandle valgte medisinske tilstander.
Enzymet DPP-IV (dipeptidylpeptidase IV), også kjent som CD26, er en serinprotease som er kjent for å føre til spaltning av et dipeptid fra den N-terminale enden av flere proteiner som på sin N-terminale ende har et prolin- eller alaninresiduum. På grunn av denne egenskapen griper DPP IV-hemmere inn i plasmanivået av bioaktive peptider, innbefattende peptidet GLP-1, og er ansett for å være lovende medikamenter for behandling av diabetes mellitus.
I forsøk på å fremstille farmasøytiske preparater av valgte DPP IV-hemmere, er det blitt observert at DPP IV-hemmerne med en primær eller sekundær aminogruppe viser uforlikelighet, nedbrytningsproblemer eller ekstraksjonsproblemer med flere vanlige tilsetningsmidler, så som mikrokrystallinsk cellulose, natriumstivelsesglykolat, croscarmellose-natrium, vinsyre, sitronsyre, glukose, fruktose, sakkarose, laktose, maltodekstriner. Selv om forbindelsene selv er meget stabile, reagerer de med mange tilsetningsmidler anvendt i faste doseformer og med urenheter i tilsetningsmidler, spesielt i tett kontakt som det er i tabletter og ved et høyt tilsetningsmiddel/medikament-forhold. Aminogruppen synes å reagere med reduserende sukkere og med andre reaktive karbonylgrupper, og med karboksylsyre-funksjonelle grupper dannet for eksempel på overflaten av mikrokrystallinsk cellulose ved oksidasjon. Disse uforutsette vanskelighetene er primært observert i de lave doseområdene som er nødvendig på grunn av den overraskende virkningsevnen til de valgte hemmerne. Således er det nødvendig med farmasøytiske preparater til å løse disse tekniske problemene forbundet med den uventede virkningsevnen til valgte DPP IV-hemmerforbindelser.
Et farmasøytisk preparat ifølge foreliggende oppfinnelse er ment for behandling for å oppnå glykemisk kontroll hos en pasient med type 1 eller type 2 diabetes mellitus, og omfatter en DPP IV-hemmer med en aminogruppe, spesielt en fri eller primær aminogruppe, som en aktiv bestanddel, et første og andre fortynningsmiddel, et bindemiddel, et desintegreringsmiddel og et glattemiddel. Et ytterligere desintegreringsmiddel og et ytterligere flytfremmende middel er en ytterligere mulighet. I tillegg kan preparatene anvendes for å behandle revmatoid artritt, fedme og osteoporose, så vel som til å understøtte allograft-transplantasjon.
Fortynningsmidler egnet for et farmasøytisk preparat ifølge oppfinnelsen, er cellulosepulver, dibasisk vannfritt kalsiumfosfat, dibasisk kalsiumfosfat-dihydrat, erytritol, lav-substituert hydroksypropylcellulose, mannitol, pregelatinert stivelse eller xylitol. Blant disse fortynningsmidlene er mannitol og pregelatinert stivelse foretrukket.
Fortynningsmidler foretrukket som det andre fortynningsmiddel, er ovennevnte fortynningsmidlene, pre-gelatinert stivelse og lav-substituert hydroksypropylcellulose (L-HPC) som viser ytterligere bindemiddel-egenskaper.
Glattemidler egnet for et farmasøytisk preparat ifølge oppfinnelsen, er talk, polyetylenglykol, kalsiumbehenat, kalsiumstearat, hydrogenert ricinusolje eller magnesiumstearat. Det foretrukne glattemiddel er magnesiumstearat.
Bindemidler egnet for et farmasøytisk preparat ifølge oppfinnelsen, er copovidon (kopolymerisater av vinylpyrrolidon med andre vinylderivater), hydroksypropylmetylcellulose (HPMC), hydroksypropylcellulose (HPC), polyvinylpyrrolidon (povidon), pregelatinert stivelse, lav-substituert hydroksypropylcellulose (L-HPC), idet copovidon og pregelatinert stivelse er foretrukket.
Ovennevnte bindemidler, pregelatinert stivelse og L-HPC viser ytterligere fortynningsmiddel- og desintegreringsmiddel-egenskaper, og kan også anvendes som det andre fortynningsmiddel eller desintegreringsmiddel.
Desintegreringsmidler egnet for et farmasøytisk preparat ifølge foreliggende oppfinnelse, er maisstivelse, crospovidon, lav-substituert hydroksypropylcellulose (L-HPC) eller pregelatinert stivelse, idet maisstivelse er foretrukket.
Som et eventuelt flytfremmende middel kan kolloidalt silisiumdioksid anvendes.
Et eksempel på et preparat ifølge foreliggende oppfinnelse, omfatter fortynningsmidlet mannitol, pregelatinert stivelse som et fortynningsmiddel med ytterligere bindemiddel-egenskaper, bindemidlet copovidon, desintegreringsmidlet maisstivelse, og magnesiumstearat som glattemidlet.
Doseformer fremstilt med et farmasøytisk preparat ifølge foreliggende oppfinnelse, inneholder aktive bestanddeler i doseområder på 0,1-100 mg. Foretrukne doser er 0,5 mg, 1 mg, 2,5 mg, 5 mg og 10 mg.
Typiske farmasøytiske preparater omfatter (vekt%):
0,5-20 % aktiv bestanddel,
40-88 % fortynningsmiddel 1,
3-40 % fortynningsmiddel 2,
1-5 % bindemiddel,
5-15 % desintegreringsmiddel, og
0,1-4 % glattemiddel.
Foretrukne farmasøytiske preparater omfatter (vekt%):
0,5-7 % aktiv bestanddel,
50-75 % fortynningsmiddel 1,
5-15 % fortynningsmiddel 2,
2-4 % bindemiddel,
8-12 % desintegreringsmiddel, og
0,5-2 % glattemiddel.
De farmasøytiske preparatene ifølge oppfinnelsen er ment for oral anvendelse, og kan anvendes i doseformen kapsel, tablett eller film-belagt tablett. Typisk representerer filmbelegget 2-4%, fortrinnsvis 3%, av preparatet, og omfatter et film-dannende middel, en mykner, et glidemiddel og eventuelt ett eller flere pigmenter. Et eksempel på et belegningspreparat kan omfatte hydroksypropylmetylcellulose (HPMC), polyetylenglykol (PEG), talk, titandioksid og eventuelt jernoksid.
Foretrukne aktive bestanddeler i sammenheng med foreliggende oppfinnelse er DPP IV-hemmere med en primær aminogruppe, og salter derav, så som en hvilken som helst DPP IV-hemmer, og et salt derav, definert med formel (I):
eller formel (II):
hvor R1 er ([1,5]naftyridin-2-yl)metyl, (kinazolin-2-yl)metyl], (kinoksalin-6-yl)metyl, (4-metylkinazolin-2-yl)metyl, 2-cyanobenzyl, (3-cyanokinolin-2-yl)metyl, (3-cyanopyridin-2-yl)metyl, (4-metylpyrimidin-2-yl)metyl eller (4,6-dimetylpyrimidin-2-yl)-metyl og R2 er 3-(R)-aminopiperidin-1-yl, (2-amino-2-metylpropyl)metylamino eller (2-(S)-aminopropyl)metylamino.
Foretrukne DPP IV-hemmerforbindelser er følgende forbindelser, og salter derav:
- 1-[(4-metylkinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-(3-(R)-aminopiperidin-1-yl)xantin (sammenlign med WO 2004/018468, eksempel 2(142):
- 1-[([1,5]naftyridin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)xantin (sammenlign med WO 2004/018468, eksempel 2(252)):
- 1-[(kinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)-xantin (sammenlign med WO 2004/018468, eksempel 2(80)):
- 2-((R)-3-aminopiperidin-1-yl)-3-(but-2-yinyl)-5-(4-metylkinazolin-2-ylmetyl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-on (sammenlign med WO 2004/050658, eksempel 136):
- 1-[(4-metylkinazolin-2-yl)metyl]-3-metyl-7-(2-butyin-1-yl)-8-[(2-amino-2-metylpropyl)metylamino]xantin (sammenlign med WO 2006/029769, eksempel 2(1)):
- 1-[(3-cyanokinolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)xantin (sammenlign med WO 2005/085246, eksempel 1(30)):
- 1-(2-cyanobenzyl)-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)-xantin (sammenlign med WO 2005/085246, eksempel 1(39)):
- 1-[(4-metylkinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-[(S)-(2-aminopropyl)metylamino]xantin (sammenlign med WO 2006/029769, eksempel 2(4)):
- 1-[(3-cyanopyridin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)xantin (sammenlign med WO 2005/085246, eksempel 1(52)):
- 1-[(4-metylpyrimidin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)xantin (sammenlign med WO 2005/085246, eksempel 1(81)):
- 1-[(4,6-dimetylpyrimidin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)xantin (sammenlign med WO 2005/085246, eksempel 1(82)):
- 1-[(kinoksalin-6-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)xantin (sammenlign med WO 2005/085246, eksempel 1(83)):
For å fremstille preparater ifølge oppfinnelsen kan et granulat fremstilles ved en våtgranuleringsprosess. Alternative metoder for granulering av en aktiv bestanddel og tilsetningsmidler med en granuleringsvæske, er fluidsjikt-granulering eller ett-kar-granulering.
I våtgranuleringsprosessen er granuleringsvæsken et løsningsmiddel, så som vann, etanol, metanol, isopropanol, aceton, fortrinnsvis renset vann, og inneholder et bindemiddel, så som copovidon. Løsningsmidlet er en flyktig komponent som ikke forblir i sluttproduktet. Den aktive bestanddelen og de andre tilsetningsmidlene, med unntak av glattemidlet, blir forhåndsblandet og granulert med den vandige granuleringsvæsken ved anvendelse av en høy-skjærkraft-granulator. Våtgranuleringstrinnet følges av et eventuelt våt-siktingstrinn, tørking og tørrsikting av granulene. Deretter kan for eksempel en fluidsjikt-tørker anvendes for tørking.
De tørkede granulene blir siktet gjennom en passende sikt. Etter tilsetning av de andre tilsetningsmidlene, med unntak av glattemidlet, blir blandingen blandet i en egnet konvensjonell blandemaskin, så som en frifallsblandemaskin, fulgt av tilsetning av glattemidlet, så som magnesiumstearat, og endelig blanding i blandemaskinen.
Således omfatter et eksempel på en våtgranuleringsfremgangsmåte for fremstilling av et farmasøytisk preparat ifølge foreliggende oppfinnelse:
a. oppløsning av et bindemiddel, så som copovidon, i et løsningsmiddel, så som renset vann, ved omgivelsestemperatur, for å få en granuleringsvæske; b. blanding av en DPP IV-hemmer, et fortynningsmiddel og et desintegreringsmiddel i en egnet blandemaskin, for å få en forhåndsblanding;
c. fukting av forhåndsblandingen med granuleringsvæsken og deretter granulering av den fuktede forhåndsblandingen, for eksempel i en høy-skjærkraftblandemaskin;
d. eventuelt sikting av den granulerte forhåndsblandingen gjennom en sikt med en maskestørrelse på minst 1,0 mm, og fortrinnsvis 3 mm;
e. tørking av granulatet ved en innløpsluft-temperatur på ca.40-75°C, og fortrinnsvis 55-65°C, for eksempel i en fluidsjikt-tørker, inntil den ønskede tørketapverdien i området 1-5 % blir oppnådd;
f. fjerning av klumper i det tørkede granulatet, for eksempel ved sikting gjennom en sikt med en maskestørrelse på 0,6 mm-1,6 mm, fortrinnsvis 1,0 mm; og
g. tilsetning av fortrinnsvis siktet glattemiddel til granulatet for endelig blanding, for eksempel i en terning- (”cube”) blandemaskin.
I en alternativ fremgangsmåte kan endel av tilsetningsmidlene, så som endel av et desintegreringsmiddel (for eksempel maisstivelse) eller et fortynningsmiddel (for eksempel pregelatinert stivelse) eller et ytterligere desintegreringsmiddel (crospovidon), tilsettes ekstragranulært før endelig blanding av trinn g.
I en annen alternativ versjon av fremgangsmåten blir granulatet produsert i trinn a til e produsert i en ett-kar-høy-skjærkraft-granuleringsprosess og påfølgende tørking i en ett-kar-granulator.
For fremstilling av kapsler blir den endelige blandingen videre fylt i kapsler. For fremstilling av tabletter eller tablettkjerner blir den endelige blandingen videre sammenpresset til tabletter med den ønskede tablettkjernevekten med passende størrelse og trykkfsthet, ved anvendelse av en passende tablett presse.
For fremstilling av film-belagte tabletter blir det fremstilt en beleggsuspensjon, og de sammenpressede tablettkjernene blir belagt med beleggsuspensjonen til en vektøkning på ca.2-4 %, fortrinnsvis ca.3%, ved anvendelse av en standard filmbestrykningsmaskin. Filmbelegg-løsningsmidlet er en flyktig komponent som ikke forblir i sluttproduktet. For å redusere den nødvendige mengden av glattemiddel i tablettene, er det en mulighet å anvende et ytre glattesystem.
Eksempler.
Eksempel 1 - Formulering for direkte sammenpressing.
En aktiv DPP IV-hemmer-bestanddel med en primær aminogruppe og alle andre tilsetningsmidler, med unntak av magnesiumstearat, blir blandet i en høyskjærkraft-blandemaskin. Denne forhåndsblandingen blir siktet gjennom en 1 mm sikt. Etter tilsetning av magnesiumstearat blir forhåndsblandingen blandet i en frifallsblandemaskin, hvilket gir den endelige blandingen. Den endelige blandingen blir presset til tabletter ved anvendelse av en egnet tablettpresse. Følgende preparater kan oppnås:
Eksempel 2 - Alternativ formulering for direkte sammenpressing.
En aktiv DPP IV-hemmer-bestanddel med en primær aminogruppe og alle andre tilsetningsmidler, med unntak av magnesiumstearat, blir blandet i en høyskjærkraft-blandemaskin. Denne forhåndsblandingen blir siktet gjennom en 1 mm sikt. Etter tilsetning av magnesiumstearat blir forhåndsblandingen blandet i en frifallsblandemaskin for å få den endelige blandingen. Den endelige blandingen blir presset til tabletter ved anvendelse av en egnet tablettpresse. Følgende preparater kan oppnås:
Eksempel 3 - Tablettformulering.
Copovidon blir oppløst i renset vann ved omgivelsestemperatur for å få en granuleringsvæske. En aktiv DPP IV-hemmer-bestanddel med en primær aminogruppe, mannitol og endel av den pregelatinerte stivelsen blir blandet i en egnet blandemaskin for å få en forhåndsblanding. Forhåndsblandingen blir fuktet med granuleringsvæsken og deretter granulert. Det fuktige granulatet blir eventuelt siktet gjennom en sikt med en maskestørrelse på 1,6-3,0 mm. Granulatet blir tørket ved 55 °C i en egnet tørker til et gjenværende fuktighetsinnhold svarende til 2-5 % tap ved tørking. Det tørkede granulatet blir siktet gjennom en sikt med en maskestørrelse på 1,0 mm. Granulatet blir blandet med endel av den pregelatinerte stivelsen i en egnet blandemaskin. Magnesiumstearat blir tilsatt til denne blandingen etter at den er blitt sendt gjennom en 1,0 mm sikt for fjerning av klumper. Deretter blir den endelige blandingen produsert ved endelig blanding i en egnet blandemaskin og presset til tabletter. Følgende tablettpreparat kan oppnås:
Eksempel 4 - Belagt tablett-formulering.
Copovidon blir oppløst i renset vann ved omgivelsestemperatur for å få en granuleringsvæske. En aktiv DPP IV-hemmer-bestanddel med en primær aminogruppe, mannitol, pregelatinert stivelse og maisstivelse blir blandet i en egnet blandemaskin for å få forhåndsblandingen. Forhåndsblandingen blir fuktet med granuleringsvæsken og deretter granulert ved anvendelse av en høy-skjærkraftblandemaskin. Det fuktige granulatet blir eventuelt siktet gjennom en sikt med en maskestørrelse på 1,6-3,0 mm. Granulatet blir tørket ved ca.60 °C i en fluidsjikttørker inntil en tørketapverdi på 2-4 % blir oppnådd. Den endelige blandingen blir presset til tablettkjerner.
Hydroksypropylmetylcellulose, polyetylenglykol, talk, titandioksid og jernoksid blir suspendert i renset vann i en egnet blandemaskin ved omgivelsestemperatur, for å få en beleggsuspensjon. Tablettkjernene blir belagt med beleggsuspensjonen til en vektøkning på ca.3 % for å få film-belagte tabletter. Følgende tablettpreparater kan oppnås:
Eksempel 5 - Tablettformulering.
Copovidon blir oppløst i renset vann ved omgivelsestemperatur for å få en granuleringsvæske. En aktiv DPP IV-hemmer-bestanddel med en primær aminogruppe, mannitol og pregelatinert stivelse blir blandet i en egnet blandemaskin for å få en forhåndsblanding. Forhåndsblandingen blir fuktet med granuleringsvæsken og deretter granulert. Det fuktige granulatet blir eventuelt siktet gjennom en egnet sikt. Granulatet blir tørket ved ca.50 °C i en egnet tørker inntil en tørketapverdi på 3-5% blir oppnådd. Det tørkede granulatet blir siktet gjennom en sikt med en maskestørrelse på 1,0 mm.
Magnesiumstearat blir ført gjennom en 1,0 mm sikt og tilsatt til granulatet. Deretter blir den endelige blandingen produsert ved endelig blanding i en egnet blandemaskin, og den endelige blandingen blir presset til tabletter. Følgende tablettpreparater kan oppnås:
Eksempel 6 - Varianter av tablettformulering.
Copovidon blir oppløst i renset vann ved omgivelsestemperatur for å få en granuleringsvæske. En aktiv DPP IV-hemmer-bestanddel med en primær aminogruppe og endel av mannitol, pregelatinert stivelse og maisstivelse blir blandet i en egnet blandemaskin for å få en forhåndsblanding. Forhåndsblandingen blir fuktet med granuleringsvæsken og deretter granulert. Det fuktige granulatet blir siktet gjennom en egnet sikt. Granulatet blir tørket ved en innløpsluft-temperatur på ca.
60 °C i en fluidsjikt-tørker inntil en tørketapverdi på 1-4 % blir oppnådd. Det tørkede granulatet blir siktet gjennom en sikt med en maskestørrelse på 1,0 mm.
Magnesiumstearat blir ført gjennom en sikt for å fjerne klumper og tilsatt til granulatet. I tillegg blir den gjenværende del av tilsetningsmidlene tilsatt ekstragranulært i dette fremgangsmåtetrinnet. Deretter blir den endelige blandingen produsert ved endelig blanding i en egnet blandemaskin og presset til tablettkjerner.
Hydroksypropylmetylcellulose, polyetylenglykol, talk, titandioksid og jernoksid blir suspendert i renset vann i en egnet blandemaskin ved omgivelsestemperatur for å få en beleggsuspensjon. Tablettkjernene blir belagt med beleggsuspensjonen til en vektøkning på ca.3 % for å få film-belagte tabletter. Følgende formuleringsvarianter kan oppnås:
Eksempel 6.1 - Formuleringsvarianter med ekstragranulære tilsetningsmidler.
Eksempel 6.2 - Formuleringsvarianter med ytterligere ekstragranulært desintegreringsmiddel.
Eksempel 6.3 - Høy dose-formuleringer D.
Claims (14)
1. Farmasøytisk preparat omfattende som en aktiv bestanddel en DPP IV inhibitorforbindelse med en aminogruppe valgt fra
• 1-[(4-metyl-kinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-(3-(R)-aminopiperidin-1-yl)-xanthin,
• 1-[([1,5]naftyridin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin,
• 1-[(Kinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin,
• 2-((R)-3-amino-piperidin-1-yl)-3-(but-2-yinyl)-5-(4-metyl-kinazolin-2-ylmetyl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-on,
• 1-[(4-metyl-kinazolin-2-yl)metyl]-3-metyl-7-(2-butyin-1-yl)-8-[(2-amino-2-metylpropyl)-metylamino]-xanthin,
• 1-[(3-cyano-kinolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin,
• 1-(2-cyano-benzyl)-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin,
• 1-[(4-metyl-kinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-[(S)-(2-aminopropyl)-metylamino]-xanthin,
• 1-[(3-cyano-pyridin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin,
• 1-[(4-metyl-pyrimidin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)-xanthin,
• 1-[(4,6-dimetyl-pyrimidin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-aminopiperidin-1-yl)-xanthin og
• 1-[(kinoksalin-6-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin,
eller et salt derav,
et første fortynningsmiddel som er mannitol, et andre fortynningsmiddel som er pregelatinert stivelse, et bindemiddel som er copovidon, et desintegreringsmiddel som er maisstivelse og et glattemiddel som er magnesiumstearat.
2. Farmasøytisk preparatet ifølge krav 1, hvor DPP IV inhibitoren er 1-[(4-metylkinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthin.
3. Farmasøytisk preparat ifølge krav 1 eller 2, omfattende:
0,5-20 % aktiv bestanddel,
40-88 % fortynningsmiddel 1,
3-40 % fortynningsmiddel 2,
1-5 % bindemiddel,
5-15 % desintegreringsmiddel, og
0,1-4 % glattemiddel.
4. Farmasøytisk preparat ifølge krav 1 eller 2, omfattende:
0,5-7 % aktiv bestanddel,
50-75 % fortynningsmiddel 1,
5-15 % fortynningsmiddel 2,
2-4 % bindemiddel,
8-12 % desintegreringsmiddel, og
0,5-2 % glattemiddel.
5. Farmasøytisk preparat ifølge krav 1 eller 2, i doseformen kapsel, tablett eller film-belagt tablett.
6. Farmasøytisk preparat ifølge krav 5, omfattende 2-4 % filmbelegg.
7. Farmasøytisk preparat ifølge krav 5, hvor filmbelegget omfatter et filmdannende middel, en mykner, et flytfremmende middel og eventuelt ett eller flere pigmenter.
8. Farmasøytisk preparat ifølge krav 7, hvor filmbelegget omfatter hydroksypropylmetylcellulose (HPMC), polyetylenglykol (PEG), talk, titandioksid og jernoksid.
9. Fremgangsmåte for fremstilling av et farmasøytisk preparat ifølge krav 1 eller 2, omfattende:
a. oppløsning av et bindemiddel i et løsningsmiddel for å få en granuleringsvæske;
b. blanding av en DPP IV-hemmer, fortynningsmidlene og desintegreringsmidlet for å oppnå en forhåndsblanding;
c. fukting av forhåndsblandingen med granuleringsvæsken og deretter granulering av den fuktede forhåndsblandingen;
d. eventuelt sikting av den granulerte forhåndsblandingen gjennom en sikt med en maskestørrelse på minst 1,0 mm;
e. tørking av granulatet ved ca.40-75°C inntil den ønskede tørketapverdien i området 1-5 % blir oppnådd;
f. sikting av det tørkede granulatet gjennom en sikt med en maskestørrelse på minst 0,6 mm;
g. tilsetning av glattemiddel til granulatet for endelig blanding.
10. Fremgangsmåte ifølge krav 9, videre omfattende:
h. sammenpressing av den endelige blandingen til tablettkjerner;
i. fremstilling av en beleggsuspensjon;
j. belegning av tablettkjernene med beleggsuspensjonen til en vektøkning på ca.2-4 % for å få film-belagte tabletter.
11. Fremgangsmåte ifølge krav 9 eller 10, hvor DPP IV inhibitoren er 1-[(4-metyl-kinazolin-2-yl)metyl]-3-metyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthin.
12. Fremgangsmåte ifølge krav 9, hvor endel av tilsetningsmidlene blir tilsatt ekstragranulære før den endelige blandingen i trinn g.
13. Fremgangsmåte ifølge krav 9, hvor granulatet produsert i trinn a-e blir produsert i en ett-kar-høy-skjærkraft-granuleringsprosess og påfølgende tørking i en ett-kar-granulator.
14. Doseform fremstilt med det farmasøytiske preparatet ifølge krav 1 eller 2, inneholdende den aktive bestanddel i en dose på 0,5 mg, 1 mg, 2,5 mg, 5 mg eller 10 mg.
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Families Citing this family (114)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
US7495005B2 (en) * | 2002-08-22 | 2009-02-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, their preparation and their use in pharmaceutical compositions |
US7482337B2 (en) * | 2002-11-08 | 2009-01-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions |
US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
US7439370B2 (en) | 2004-05-10 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides |
DE102004030502A1 (de) | 2004-06-24 | 2006-01-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel |
DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
US7772191B2 (en) | 2005-05-10 | 2010-08-10 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein |
DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
EP1852108A1 (en) * | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
MX2008014024A (es) | 2006-05-04 | 2008-11-14 | Boehringer Ingelheim Int | Formas poliformas. |
PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
WO2007143705A2 (en) | 2006-06-06 | 2007-12-13 | Intra-Cellular Therapies, Inc. | Organic compounds |
JP2010500326A (ja) | 2006-08-08 | 2010-01-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 糖尿病の治療のためのdpp−iv阻害剤としてのピロロ[3,2−d]ピリミジン |
EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
PE20090938A1 (es) | 2007-08-16 | 2009-08-08 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un derivado de benceno sustituido con glucopiranosilo |
JP5701608B2 (ja) | 2007-12-06 | 2015-04-15 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 有機化合物 |
PE20140960A1 (es) * | 2008-04-03 | 2014-08-15 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
KR20200118243A (ko) | 2008-08-06 | 2020-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
WO2010018866A1 (ja) * | 2008-08-14 | 2010-02-18 | 杏林製薬株式会社 | 安定化された医薬組成物 |
WO2010029089A2 (en) | 2008-09-10 | 2010-03-18 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
JP5694773B2 (ja) * | 2008-09-30 | 2015-04-01 | テバ製薬株式会社 | 圧縮成型製剤およびその製造方法 |
US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
JP5710493B2 (ja) | 2008-12-06 | 2015-04-30 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 有機化合物 |
MX2011005935A (es) | 2008-12-06 | 2011-12-16 | Intra Cellular Therapies Inc | Compuestos organicos. |
MX2011005934A (es) | 2008-12-06 | 2011-12-16 | Intra Cellular Therapies Inc | Compuestos organicos. |
WO2010072776A1 (en) | 2008-12-23 | 2010-07-01 | Boehringer Ingelheim International Gmbh | Salt forms of organic compound |
AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
WO2010079433A2 (en) * | 2009-01-07 | 2010-07-15 | Glenmark Pharmaceuticals, S.A. | Pharmaceutical composition that includes a dipeptidyl peptidase-iv inhibitor |
UY32048A (es) | 2009-01-08 | 2010-03-26 | Boehringer Ingelheim Int | Derivados sustituido de 1-(sustituido)-3-metil-7-(sustituido)-8-(3-(R)-amino-piperidin-1-il)cantina y derivados sustituidos de 1-(sustituido) - 4 - fluoropirrolidin- 2 - carbonitrilo y sus sales famacéuticamente aceptables como inhibidores de DPP-4 y aplicaciones. |
TWI466672B (zh) | 2009-01-29 | 2015-01-01 | Boehringer Ingelheim Int | 小兒科病人糖尿病之治療 |
UA102429C2 (ru) | 2009-02-13 | 2013-07-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | Фармацевтическая композиция, которая включает ингибитор sglt-2, ингибитор дпп-iv и другой антидиабетический агент, и ее применение |
NZ619520A (en) * | 2009-02-13 | 2015-06-26 | Boehringer Ingelheim Int | Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics |
UY32427A (es) | 2009-02-13 | 2010-09-30 | Boheringer Ingelheim Internat Gmbh | Composicion farmaceutica, forma farmaceutica, procedimiento para su preparacion, metodos de tratamiento y usos de la misma |
LT3351240T (lt) | 2009-05-19 | 2019-06-10 | Celgene Corporation | 4-amino-2-(2,6-dioksopiperidin-3-il)izoindolin-1,3-diono kompozicijos |
EA020798B1 (ru) | 2009-09-30 | 2015-01-30 | Бёрингер Ингельхайм Интернациональ Гмбх | СПОСОБ ПОЛУЧЕНИЯ КРИСТАЛЛИЧЕСКОЙ ФОРМЫ 1-ХЛОР-4-(β-D-ГЛЮКОПИРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГИДРОФУРАН-3-ИЛОКСИ)БЕНЗИЛ]БЕНЗОЛА |
BR112012007085B8 (pt) | 2009-09-30 | 2021-05-25 | Boehringer Ingelheim Int | processos para a preparação de derivados de benzil-benzeno substituídos com glicopiranosila |
UY32919A (es) | 2009-10-02 | 2011-04-29 | Boehringer Ingelheim Int | Composición farmacéutica, forma de dosificación farmacéutica, procedimiento para su preparación, mé todos para su tratamiento y sus usos |
WO2011039367A2 (en) | 2009-10-02 | 2011-04-07 | Boehringer Ingelheim International Gmbh | Therapeutic uses of pharmaceutical compositions |
CN102753161A (zh) | 2009-11-27 | 2012-10-24 | 贝林格尔.英格海姆国际有限公司 | 基因型糖尿病患者利用dpp-iv抑制剂例如利拉利汀的治疗 |
TWI418370B (zh) | 2009-12-18 | 2013-12-11 | Mitsubishi Tanabe Pharma Corp | 溶出安定性製劑 |
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
JP5031054B2 (ja) * | 2010-03-18 | 2012-09-19 | 信越化学工業株式会社 | 低置換度ヒドロキシプロピルセルロース及びこれを含む固形製剤 |
WO2011113947A1 (en) | 2010-03-18 | 2011-09-22 | Boehringer Ingelheim International Gmbh | Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions |
MX2012012438A (es) * | 2010-05-05 | 2012-11-29 | Boehringer Ingelheim Int | Formulaciones farmaceuticas que comprenden pioglitazona y linagliptina. |
ES2935300T3 (es) * | 2010-05-05 | 2023-03-03 | Boehringer Ingelheim Int | Combiterapia |
WO2011153136A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
US9371327B2 (en) | 2010-05-31 | 2016-06-21 | Intra-Cellular Therapies, Inc. | PDE1 inhibitor compounds |
WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
CN106975074A (zh) | 2010-06-24 | 2017-07-25 | 勃林格殷格翰国际有限公司 | 糖尿病治疗 |
TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
UY33937A (es) | 2011-03-07 | 2012-09-28 | Boehringer Ingelheim Int | Composiciones farmacéuticas que contienen inhibidores de dpp-4 y/o sglt-2 y metformina |
EP2683700B1 (de) | 2011-03-08 | 2015-02-18 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
EP2707368B1 (en) | 2011-05-10 | 2016-02-03 | Sandoz AG | Polymorph of linagliptin benzoate |
WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
WO2013010964A1 (en) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions |
WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
US20130172244A1 (en) | 2011-12-29 | 2013-07-04 | Thomas Klein | Subcutaneous therapeutic use of dpp-4 inhibitor |
US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
US9192617B2 (en) | 2012-03-20 | 2015-11-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
WO2013171167A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
JP6374862B2 (ja) | 2012-05-24 | 2018-08-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 自己免疫性糖尿病、特に、ladaの治療に使用するためのdpp−4阻害剤としてのキサンチン誘導体 |
WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
EP2854824A1 (en) | 2012-05-25 | 2015-04-08 | Boehringer Ingelheim International GmbH | Use of keratinocytes as a biologically active substance in the treatment of wounds, such as diabetic wounds, optionally in combination with a dpp-4 inhibitor |
TWI580444B (zh) | 2012-06-05 | 2017-05-01 | 武田藥品工業股份有限公司 | 固態製劑 |
EA027274B1 (ru) * | 2012-08-13 | 2017-07-31 | Сандоз Аг | Стабильная фармацевтическая композиция, содержащая 8-[(3r)-3-амино-1-пиперидинил]-7-(2-бутин-1-ил)-3,7-дигидро-3-метил-1-[(4-метил-2-хиназолинил)метил]-1н-пурин-2,6-дион или его фармацевтически приемлемую соль |
US20150246117A1 (en) | 2012-09-24 | 2015-09-03 | Ulf Eriksson | Treatment of type 2 diabetes and related conditions |
JP6283313B2 (ja) * | 2012-09-27 | 2018-02-21 | 株式会社三和化学研究所 | アナグリプチン含有医薬組成物 |
JP6283314B2 (ja) * | 2012-09-27 | 2018-02-21 | 株式会社三和化学研究所 | アナグリプチン含有固形製剤 |
JP6309895B2 (ja) * | 2012-09-27 | 2018-04-11 | 株式会社三和化学研究所 | アナグリプチン含有製剤 |
EP2911655A1 (en) | 2012-10-24 | 2015-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Tpl2 kinase inhibitors for preventing or treating diabetes and for promoting -cell survival |
JP6283316B2 (ja) * | 2012-10-26 | 2018-02-21 | 株式会社三和化学研究所 | アナグリプチン含有固形製剤 |
WO2014080384A1 (en) | 2012-11-26 | 2014-05-30 | Ranbaxy Laboratories Limited | Pharmaceutical composition of linagliptin |
CA2903577C (en) | 2013-03-15 | 2023-10-17 | Boehringer Ingelheim International Gmbh | Use of linagliptin in cardio- and renoprotective antidiabetic therapy |
US20140303097A1 (en) | 2013-04-05 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
US11813275B2 (en) | 2013-04-05 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
HUE041709T2 (hu) | 2013-04-05 | 2019-05-28 | Boehringer Ingelheim Int | Az empagliflozin terápiás alkalmazásai |
HRP20220365T1 (hr) | 2013-04-18 | 2022-05-13 | Boehringer Ingelheim International Gmbh | Farmaceutski pripravak, postupci za liječenje i njegove uporabe |
EP2848241A1 (en) | 2013-09-12 | 2015-03-18 | Sanovel Ilac Sanayi ve Ticaret A.S. | Effervescent formulations of linagliptin |
TR201310724A2 (tr) | 2013-09-12 | 2015-03-23 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Linagliptinin farmasotik formulasyonları. |
EP2848242A1 (en) | 2013-09-12 | 2015-03-18 | Sanovel Ilac Sanayi ve Ticaret A.S. | Orally disintegrating formulations of Linagliptin |
WO2015110962A1 (en) | 2014-01-21 | 2015-07-30 | Wockhardt Limited | Solid oral pharmaceutical compositions comprising fixed dose combination of metformin and linagliptin or salts thereof |
US9526728B2 (en) | 2014-02-28 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Medical use of a DPP-4 inhibitor |
US20150283248A1 (en) * | 2014-04-02 | 2015-10-08 | Aurobindo Pharma Ltd. | Pharmaceutical compositions of Linagliptin and process for preparation thereof |
US9546175B2 (en) | 2014-08-07 | 2017-01-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
CN105878349A (zh) * | 2014-11-28 | 2016-08-24 | 于凯 | 一种预防和治疗糖尿病引起的骨质疏松的组合物 |
WO2016151018A1 (en) | 2015-03-24 | 2016-09-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and pharmaceutical composition for use in the treatment of diabetes |
CA2987850A1 (en) * | 2015-06-17 | 2016-12-22 | Hexal Aktiengesellschaft | Alogliptin formulation |
JP6839708B2 (ja) * | 2015-10-09 | 2021-03-10 | ヘクサル・アクチェンゲゼルシャフトHexal AG | 8−[(3r)−3−アミノ−1−ピペリジニル]−7−(2−ブチン−1−イル)−3,7−ジヒドロ−3−メチル−1−[4−メチル−2−キナゾリニル)メチル]−1h−プリン−2,6−ジオンまたは薬学上許容できるその塩を含有する医薬組成物 |
EP3156048A1 (en) | 2015-10-13 | 2017-04-19 | Galenicum Health S.L. | Stable pharmaceutical composition of linagliptin in the form of immediate release tablets |
US9727330B2 (en) * | 2015-11-25 | 2017-08-08 | Red Hat, Inc. | Source to image transformation pipeline for a platform-as-a-service system |
CN105853382B (zh) * | 2016-05-19 | 2019-07-19 | 广州迈达康医药科技有限公司 | 一种利格列汀口崩片及其制备方法 |
BR112018072401A2 (pt) | 2016-06-10 | 2019-02-19 | Boehringer Ingelheim International Gmbh | combinações de linagliptina e metformina |
CN106236754A (zh) * | 2016-07-31 | 2016-12-21 | 合肥远志医药科技开发有限公司 | 一种包含利格列汀活性成分的组合物及其制备方法 |
CN106137991A (zh) * | 2016-08-01 | 2016-11-23 | 合肥远志医药科技开发有限公司 | 一种利格列汀片制粒方法 |
WO2018104263A1 (en) | 2016-12-06 | 2018-06-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of enhancing the potency of incretin-based drugs in subjects in need thereof |
WO2020009675A2 (en) * | 2018-06-01 | 2020-01-09 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Solid oral pharmaceutical compositions of linagliptin |
EP4045048A4 (en) | 2019-10-14 | 2023-05-24 | Santa Farma Ilaç Sanayi A.S. | ORAL FORMULATIONS COMPRISING SITAGLIPTIN HCI MONOHYDRATE WITH ENHANCED PHARMACEUTICAL CHARACTERISTICS |
WO2021109970A1 (zh) * | 2019-12-02 | 2021-06-10 | 成都苑东生物制药股份有限公司 | 一种黄嘌呤衍生物药物组合物及其制备方法 |
CN117858703A (zh) | 2021-07-22 | 2024-04-09 | 新梅斯托克公司 | 用于制备包含利格列汀和盐酸二甲双胍的药物组合物的方法 |
KR20230126664A (ko) | 2022-02-23 | 2023-08-30 | 주식회사 제뉴원사이언스 | 리나글립틴 또는 이의 약학적으로 허용가능한 염과 메트포르민 또는 이의 약학적으로 허용가능한 염을 포함하는 약물방출이 조절된 약제학적 복합제제 |
CN115227661B (zh) * | 2022-09-22 | 2022-12-13 | 北京惠之衡生物科技有限公司 | 一种利格列汀片及其制备方法 |
WO2024091863A1 (en) | 2022-10-25 | 2024-05-02 | Starrock Pharma Llc | Combinatorial, and rotational combinatorial therapies for obesity and other diseases |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6548481B1 (en) * | 1998-05-28 | 2003-04-15 | Probiodrug Ag | Effectors of dipeptidyl peptidase IV |
WO2004018468A2 (de) * | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-amino-piperidin-1-yl]-xanthine, deren herstellung und deren verwendung als arzneimittel |
EP1537880A1 (en) * | 2002-09-11 | 2005-06-08 | Takeda Pharmaceutical Company Limited | Sustained release preparation |
Family Cites Families (469)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2056046A (en) * | 1933-05-19 | 1936-09-29 | Rhone Poulenc Sa | Manufacture of bases derived from benz-dioxane |
US2375138A (en) * | 1942-05-01 | 1945-05-01 | American Cyanamid Co | Alkamine esters of aryloxymethyl benzoic acid |
US2629736A (en) * | 1951-02-24 | 1953-02-24 | Searle & Co | Basically substituted n-alkyl derivatives of alpha, beta, beta-triarylpropionamides |
US2730544A (en) * | 1952-07-23 | 1956-01-10 | Sahyun Lab | Alkylaminoalkyl esters of hydroxycyclohexylbenzoic acid |
US2750387A (en) * | 1953-11-25 | 1956-06-12 | Searle & Co | Basically substituted derivatives of diarylaminobenzamides |
DE1211359B (de) * | 1955-11-29 | 1966-02-24 | Oreal | Oxydationsmittelfreies Kaltfaerbemittel fuer menschliches Haar |
US2928833A (en) * | 1959-03-03 | 1960-03-15 | S E Massengill Company | Theophylline derivatives |
US3174901A (en) * | 1963-01-31 | 1965-03-23 | Jan Marcel Didier Aron Samuel | Process for the oral treatment of diabetes |
US3454635A (en) * | 1965-07-27 | 1969-07-08 | Hoechst Ag | Benzenesulfonyl-ureas and process for their manufacture |
US3673241A (en) * | 1968-04-04 | 1972-06-27 | Ciba Geigy Corp | Substituted benzaldehyde guanylhydrazones |
ES385302A1 (es) | 1970-10-22 | 1973-04-16 | Miquel S A Lab | Procedimiento para la obtencion de derivados trisubstitui- dos de etilendiamina. |
DE2205815A1 (de) | 1972-02-08 | 1973-08-16 | Hoechst Ag | Piperazinderivate und verfahren zu ihrer herstellung |
JPS5512435B2 (no) * | 1972-07-01 | 1980-04-02 | ||
US4005208A (en) * | 1975-05-16 | 1977-01-25 | Smithkline Corporation | N-Heterocyclic-9-xanthenylamines |
US4061753A (en) | 1976-02-06 | 1977-12-06 | Interx Research Corporation | Treating psoriasis with transient pro-drug forms of xanthine derivatives |
AU508480B2 (en) | 1977-04-13 | 1980-03-20 | Asahi Kasei Kogyo Kabushiki Kaisha | Microcrystalline cellulose excipient and pharmaceutical composition containing thesame |
NO154918C (no) | 1977-08-27 | 1987-01-14 | Bayer Ag | Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin. |
DE2758025A1 (de) | 1977-12-24 | 1979-07-12 | Bayer Ag | Neue derivate von 3,4,5-trihydroxypiperidin, verfahren zu ihrer herstellung und ihre verwendung |
DE2929596A1 (de) | 1979-07-21 | 1981-02-05 | Hoechst Ag | Verfahren zur herstellung von oxoalkyl-xanthinen |
CY1306A (en) | 1980-10-01 | 1985-12-06 | Glaxo Group Ltd | Aminoalkyl furan derivative |
US4382091A (en) | 1981-04-30 | 1983-05-03 | Syntex (U.S.A.) Inc. | Stabilization of 1-substituted imidazole derivatives in talc |
FR2558162B1 (fr) * | 1984-01-17 | 1986-04-25 | Adir | Nouveaux derives de la xanthine, leurs procedes de preparation et les compositions pharmaceutiques les renfermant |
FI79107C (fi) * | 1984-06-25 | 1989-11-10 | Orion Yhtymae Oy | Foerfarande foer framstaellning av stabil -form av prazosinhydroklorid. |
JPS6130567A (ja) | 1984-07-23 | 1986-02-12 | Shiseido Co Ltd | 尿素の安定化法 |
JPS61124383A (ja) | 1984-11-16 | 1986-06-12 | Unitika Ltd | 固定化線維素溶解活性酵素の安定化法 |
AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
CA1242699A (en) | 1985-02-01 | 1988-10-04 | Bristol-Myers Company | Cefbuperazone and derivatives thereof |
US5258380A (en) * | 1985-06-24 | 1993-11-02 | Janssen Pharmaceutica N.V. | (4-piperidinylmethyl and -hetero)purines |
GB8515934D0 (en) * | 1985-06-24 | 1985-07-24 | Janssen Pharmaceutica Nv | (4-piperidinomethyl and-hetero)purines |
EP0223403B1 (en) | 1985-10-25 | 1993-08-04 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
US5034225A (en) | 1985-12-17 | 1991-07-23 | Genentech Inc. | Stabilized human tissue plasminogen activator compositions |
US5433959A (en) | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
DE3683760D1 (de) | 1986-03-21 | 1992-03-12 | Heumann Pharma Gmbh & Co | Kristalline, wasserfreie sigma -form von 2-(4-(2-furoyl-(2-piperazin)-1-yl)-4-amino-6,7-dimethoxychinazolinhydrochlorid und verfahren zu ihrer herstellung. |
DE3750402T3 (de) | 1986-05-05 | 1997-04-10 | Gen Hospital Corp | Insulinotropes hormon. |
US5120712A (en) | 1986-05-05 | 1992-06-09 | The General Hospital Corporation | Insulinotropic hormone |
AU619444B2 (en) | 1986-06-02 | 1992-01-30 | Nippon Chemiphar Co. Ltd. | 2-(2-aminobenzylsulfinyl)- benzimidazole derivatives |
US4968672A (en) | 1987-01-02 | 1990-11-06 | The United States Of America As Represented By The Department Of Health And Human Services | Adenosine receptor prodrugs |
US4743450A (en) | 1987-02-24 | 1988-05-10 | Warner-Lambert Company | Stabilized compositions |
JPS6440433A (en) | 1987-08-05 | 1989-02-10 | Green Cross Corp | Aqueous liquid composition of thrombin |
DE68920773T2 (de) | 1988-05-19 | 1995-05-18 | Chugai Pharmaceutical Co Ltd | Chinoloncarbonsäure-Derivate. |
US5329025A (en) * | 1988-09-21 | 1994-07-12 | G. D. Searle & Co. | 3-azido compound |
US5234897A (en) * | 1989-03-15 | 1993-08-10 | Bayer Aktiengesellschaft | Herbicidal 3-amino-5-aminocarbonyl-1,2,4-triazoles |
DE3926119A1 (de) | 1989-08-08 | 1991-02-14 | Bayer Ag | 3-amino-5-aminocarbonyl-1,2,4-triazol-derivate |
GB8906792D0 (en) | 1989-03-23 | 1989-05-10 | Beecham Wuelfing Gmbh & Co Kg | Treatment and compounds |
DE3916430A1 (de) * | 1989-05-20 | 1990-11-22 | Bayer Ag | Verfahren zur herstellung von 3-amino-5-aminocarbonyl-1,2,4-triazol-derivaten |
US5332744A (en) * | 1989-05-30 | 1994-07-26 | Merck & Co., Inc. | Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists |
US5223499A (en) * | 1989-05-30 | 1993-06-29 | Merck & Co., Inc. | 6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists |
IL94390A (en) | 1989-05-30 | 1996-03-31 | Merck & Co Inc | The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them |
FI94339C (fi) | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
HU208115B (en) | 1989-10-03 | 1993-08-30 | Biochemie Gmbh | New process for producting pleuromutilin derivatives |
FR2654935B1 (fr) * | 1989-11-28 | 1994-07-01 | Lvmh Rech | Utilisation de xanthines, eventuellement incorporees dans des liposomes, pour favoriser la pigmentation de la peau ou des cheveux. |
DE122007000050I1 (de) | 1990-02-19 | 2007-11-08 | Novartis Ag | Acylverbindungen |
KR930000861B1 (ko) | 1990-02-27 | 1993-02-08 | 한미약품공업 주식회사 | 오메프라졸 직장투여 조성물 |
ATE112491T1 (de) | 1990-09-13 | 1994-10-15 | Akzo Nobel Nv | Stabilisierte feste chemische zusammensetzungen. |
GB9020959D0 (en) | 1990-09-26 | 1990-11-07 | Beecham Group Plc | Novel compounds |
US5084460A (en) * | 1990-12-24 | 1992-01-28 | A. H. Robins Company, Incorporated | Methods of therapeutic treatment with N-(3-ouinuclidinyl)-2-hydroxybenzamides and thiobenzamides |
US5594003A (en) | 1991-02-06 | 1997-01-14 | Dr. Karl Thomae Gmbh | Tetrahydroimidazo[1,2-a]pyridin-2-yl-(benzimidazol-1-yl)-methyl-biphenyls useful as angiotensin-II antagonists |
US5591762A (en) | 1991-02-06 | 1997-01-07 | Dr. Karl Thomae Gmbh | Benzimidazoles useful as angiotensin-11 antagonists |
US5602127A (en) | 1991-02-06 | 1997-02-11 | Karl Thomae Gmbh | (Alkanesultam-1-yl)-benzimidazol-1-yl)-1yl)-methyl-biphenyls useful as angiotensin-II antagonists |
GB9109862D0 (en) | 1991-05-08 | 1991-07-03 | Beecham Lab Sa | Pharmaceutical formulations |
DE4124150A1 (de) | 1991-07-20 | 1993-01-21 | Bayer Ag | Substituierte triazole |
US5300298A (en) * | 1992-05-06 | 1994-04-05 | The Pennsylvania Research Corporation | Methods of treating obesity with purine related compounds |
GB9215633D0 (en) | 1992-07-23 | 1992-09-09 | Smithkline Beecham Plc | Novel treatment |
TW307769B (no) | 1992-07-31 | 1997-06-11 | Shionogi & Co | |
TW252044B (no) | 1992-08-10 | 1995-07-21 | Boehringer Ingelheim Kg | |
US5358941A (en) | 1992-12-02 | 1994-10-25 | Merck & Co., Inc. | Dry mix formulation for bisphosphonic acids with lactose |
DE4242459A1 (de) * | 1992-12-16 | 1994-06-23 | Merck Patent Gmbh | Imidazopyridine |
AU6087894A (en) | 1993-01-14 | 1994-08-15 | Cell Therapeutics, Inc. | Acetal or ketal substituted therapeutic compounds |
EP0638567A4 (en) | 1993-02-18 | 1995-05-10 | Kyowa Hakko Kogyo Kk | ADENOSINE INHIBITORS. |
JP3726291B2 (ja) | 1993-07-05 | 2005-12-14 | 三菱ウェルファーマ株式会社 | 安定な結晶構造を有するベンゾオキサジン化合物およびその製造法 |
FR2707641B1 (fr) | 1993-07-16 | 1995-08-25 | Fournier Ind & Sante | Composés de l'imidazol-5-carboxamide, leur procédé de préparation leurs intermédiaires et leur utilisation en thérapeutique. |
DE4339868A1 (de) | 1993-11-23 | 1995-05-24 | Merck Patent Gmbh | Imidazopyridazine |
DE4404183A1 (de) | 1994-02-10 | 1995-08-17 | Merck Patent Gmbh | 4-Amino-1-piperidylbenzoylguanidine |
US5545745A (en) | 1994-05-23 | 1996-08-13 | Sepracor, Inc. | Enantioselective preparation of optically pure albuterol |
CO4410191A1 (es) | 1994-09-19 | 1997-01-09 | Lilly Co Eli | SINTESIS DE 3-[4-(2-AMINOETOXI)BENZOIL]-2-ARIL-6- HIDROXIBENZO [b] TIOFENOS |
KR100237962B1 (ko) | 1994-10-12 | 2000-02-01 | 그린 마틴 | 신규한 벤즈옥사졸 |
GB9501178D0 (en) | 1995-01-20 | 1995-03-08 | Wellcome Found | Guanine derivative |
JPH11505241A (ja) | 1995-05-19 | 1999-05-18 | カイロサイエンス・リミテッド | キサンチン類およびこれらの治療的使用 |
JPH08333339A (ja) | 1995-06-08 | 1996-12-17 | Fujisawa Pharmaceut Co Ltd | 光学活性なピペリジン酢酸誘導体の製造法 |
GB9523752D0 (en) | 1995-11-21 | 1996-01-24 | Pfizer Ltd | Pharmaceutical formulations |
DE19543478A1 (de) | 1995-11-22 | 1997-05-28 | Bayer Ag | Kristallines Hydrochlorid von {(R)-(-)-2- N-[4-(1,1-Dioxido-3-oxo-2,3-dihydrobenzisothiazol-2-yl)-buytl]-aminomethyl}-chroman |
FR2742751B1 (fr) | 1995-12-22 | 1998-01-30 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
CA2241746A1 (en) | 1995-12-26 | 1997-07-03 | Alteon Inc. | N-acylaminoalkylhydrazinecarboximidamides |
US5891855A (en) | 1996-02-12 | 1999-04-06 | The Scripps Research Institute | Inhibitors of leaderless protein export |
DE122010000020I1 (de) * | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
TW518219B (en) | 1996-04-26 | 2003-01-21 | Chugai Pharmaceutical Co Ltd | Erythropoietin solution preparation |
US5965555A (en) | 1996-06-07 | 1999-10-12 | Hoechst Aktiengesellschaft | Xanthine compounds having terminally animated alkynol side chains |
AU1153097A (en) | 1996-06-07 | 1998-01-05 | Eisai Co. Ltd. | Stable polymorphs of donepezil (1-benzyl-4-{(5,6-dimethoxy-1-indanon)-2-yl}methylpiperidine ) hydrochloride and process for production |
US5958951A (en) | 1996-06-14 | 1999-09-28 | Novo Nordiskials | Modified form of the R(-)-N-(4,4-di(3-methylthien-2-yl)but-3-enyl)-nipecotic acid hydrochloride |
US5753635A (en) * | 1996-08-16 | 1998-05-19 | Berlex Laboratories, Inc. | Purine derivatives and their use as anti-coagulants |
ID21924A (id) | 1996-09-23 | 1999-08-12 | Lilly Co Eli | Olanzapin dihidrat d |
WO1998018770A1 (en) | 1996-10-28 | 1998-05-07 | Novo Nordisk A/S | A process for the preparation of (-)-3,4-trans-diarylchromans |
UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
ATE289517T1 (de) | 1996-11-12 | 2005-03-15 | Novo Nordisk As | Verwendung von glp-1 peptiden |
GB9623859D0 (en) | 1996-11-15 | 1997-01-08 | Chiroscience Ltd | Novel compounds |
CN1222315C (zh) | 1996-12-24 | 2005-10-12 | 拜奥根有限公司 | 稳定的液体干扰素制剂 |
DE19705233A1 (de) | 1997-02-12 | 1998-08-13 | Froelich Juergen C | Verfahren zur Herstellung einer Formulierung enthaltend Arginin |
US6011049A (en) | 1997-02-19 | 2000-01-04 | Warner-Lambert Company | Combinations for diabetes |
NZ337592A (en) | 1997-03-13 | 2001-01-26 | Hexal Ag | Stabilization of acid sensitive benzimidazoles with amino/cyclodextrin combinations |
US5972332A (en) | 1997-04-16 | 1999-10-26 | The Regents Of The University Of Michigan | Wound treatment with keratinocytes on a solid support enclosed in a porous material |
CO4750643A1 (es) | 1997-06-13 | 1999-03-31 | Lilly Co Eli | Formulacion estable de la insulina que contiene l-arginina y protamina |
US6174548B1 (en) | 1998-08-28 | 2001-01-16 | Andrx Pharmaceuticals, Inc. | Omeprazole formulation |
JP2001525413A (ja) | 1997-12-05 | 2001-12-11 | アストラゼネカ ユーケイ リミテッド | 新規化合物 |
ID21411A (id) | 1997-12-10 | 1999-06-10 | Takeda Chemical Industries Ltd | Agen untuk mengobati daya tahan glukosa yang berisiko tinggi rusak |
JPH11193270A (ja) | 1997-12-26 | 1999-07-21 | Koei Chem Co Ltd | 光学活性1−メチル−3−ピペリジンメタノールの製造方法 |
WO1999035147A1 (fr) | 1998-01-05 | 1999-07-15 | Eisai Co., Ltd. | Derives de purine et antagonistes du recepteur a2 d'adenosine utiles comme moyens de prevention/traitement du diabete |
DE04029691T1 (de) | 1998-02-02 | 2007-11-08 | Trustees Of Tufts College, Medford | Verwendung von Dipetidylpeptidasehemmer zur Regulierung des Glukosemetabolismus |
US20030013740A1 (en) | 1998-03-27 | 2003-01-16 | Martin P. Redmon | Stable dosage forms of fluoxetine and its enantiomers |
CA2326506A1 (en) | 1998-03-31 | 1999-10-07 | Nissan Chemical Industries, Ltd. | Pyridazinone hydrochloride compound and method for producing the same |
EP0950658A1 (en) | 1998-04-13 | 1999-10-20 | Takeda Chemical Industries, Ltd. | 2-Pipirazinone-1-acetic acid dihydrochloride derivative used to inhibit platelet aggregation |
US6207207B1 (en) | 1998-05-01 | 2001-03-27 | Mars, Incorporated | Coated confectionery having a crispy starch based center and method of preparation |
DE19828114A1 (de) | 1998-06-24 | 2000-01-27 | Probiodrug Ges Fuer Arzneim | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
DE69928110T2 (de) | 1998-07-15 | 2006-07-27 | Asahi Kasei Chemicals Corporation | Trägerhilfstoff |
CO5150173A1 (es) | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
IT1312018B1 (it) | 1999-03-19 | 2002-04-04 | Fassi Aldo | Procedimento migliorato per la produzione di sali non igroscopicidella l(-)-carnitina. |
WO2000066101A2 (en) | 1999-04-30 | 2000-11-09 | City Of Hope | Method of inhibiting glycation product formation |
US20040152659A1 (en) | 1999-05-12 | 2004-08-05 | Fujisawa Pharmaceutical Co. Ltd. | Method for the treatment of parkinson's disease comprising administering an A1A2a receptor dual antagonist |
EP1177797A1 (en) | 1999-05-12 | 2002-02-06 | Fujisawa Pharmaceutical Co., Ltd. | Novel use |
WO2000072799A2 (en) | 1999-05-27 | 2000-12-07 | The University Of Virginia Patent Foundation | Method and compositions for treating the inflammatory response |
ES2408784T3 (es) | 1999-05-31 | 2013-06-21 | Mitsubishi Chemical Corporation | Preparaciones liofilizadas de HGF |
DE60012520T3 (de) | 1999-06-01 | 2009-06-25 | Elan Pharma International Ltd. | Kleinmühle und verfahren dafür |
US6545002B1 (en) | 1999-06-01 | 2003-04-08 | University Of Virginia Patent Foundation | Substituted 8-phenylxanthines useful as antagonists of A2B adenosine receptors |
EP1194418A1 (de) | 1999-06-21 | 2002-04-10 | Boehringer Ingelheim Pharma KG | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
US6448323B1 (en) | 1999-07-09 | 2002-09-10 | Bpsi Holdings, Inc. | Film coatings and film coating compositions based on polyvinyl alcohol |
ES2166270B1 (es) | 1999-07-27 | 2003-04-01 | Almirall Prodesfarma Sa | Derivados de 8-fenil-6,9-dihidro-(1,2,4,)triazolo(3,4-i)purin-5-ona. |
US6515117B2 (en) | 1999-10-12 | 2003-02-04 | Bristol-Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
US6586438B2 (en) | 1999-11-03 | 2003-07-01 | Bristol-Myers Squibb Co. | Antidiabetic formulation and method |
GB9928330D0 (en) | 1999-11-30 | 2000-01-26 | Ferring Bv | Novel antidiabetic agents |
SG149676A1 (en) | 1999-12-23 | 2009-02-27 | Novartis Ag | Use of hypoglycemic agent for treating impaired glucose metabolism |
CA2396079A1 (en) | 2000-01-07 | 2001-07-19 | Transform Pharmaceuticals, Inc. | High-throughput formation, identification, and analysis of diverse solid-forms |
US6362172B2 (en) | 2000-01-20 | 2002-03-26 | Bristol-Myers Squibb Company | Water soluble prodrugs of azole compounds |
CN1977842A (zh) | 2000-01-21 | 2007-06-13 | 诺瓦提斯公司 | 含有二肽基肽酶-iv抑制剂和抗糖尿病药物的联合形式 |
JP4621326B2 (ja) * | 2000-02-01 | 2011-01-26 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | テプレノンの安定化組成物 |
AU782878B2 (en) * | 2000-02-05 | 2005-09-08 | Vertex Pharmaceuticals Incorporated | Pyrazole compositions useful as inhibitors of erk |
AU2001234114A1 (en) | 2000-02-24 | 2001-09-03 | Takeda Chemical Industries Ltd. | Drugs containing combined active ingredients |
EP1132389A1 (en) | 2000-03-06 | 2001-09-12 | Vernalis Research Limited | New aza-indolyl derivatives for the treatment of obesity |
US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
GB0006133D0 (en) | 2000-03-14 | 2000-05-03 | Smithkline Beecham Plc | Novel pharmaceutical |
JP2001278812A (ja) * | 2000-03-27 | 2001-10-10 | Kyoto Pharmaceutical Industries Ltd | 錠剤用崩壊剤及びこれを用いた錠剤 |
US6399101B1 (en) | 2000-03-30 | 2002-06-04 | Mova Pharmaceutical Corp. | Stable thyroid hormone preparations and method of making same |
ATE419036T1 (de) | 2000-03-31 | 2009-01-15 | Prosidion Ltd | Verbesserung der aktivität der inselzellen bei diabetes mellitus und dessen prävention |
AU4458401A (en) | 2000-03-31 | 2001-10-15 | Kirin Brewery | Powdery preparation for transmucosal administration containing a polymeric form of drug and exhibiting improved storage stability |
JP2001292388A (ja) | 2000-04-05 | 2001-10-19 | Sharp Corp | 再生装置 |
GB0008694D0 (en) | 2000-04-07 | 2000-05-31 | Novartis Ag | Organic compounds |
WO2001096301A1 (fr) | 2000-06-14 | 2001-12-20 | Toray Industries, Inc. | Procedes de production de derive de piperidine racemique et de production de derive de piperidine a activite optique |
US7078397B2 (en) | 2000-06-19 | 2006-07-18 | Smithkline Beecham Corporation | Combinations of dipeptidyl peptidase IV inhibitors and other antidiabetic agents for the treatment of diabetes mellitus |
GB0014969D0 (en) | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
US6689353B1 (en) | 2000-06-28 | 2004-02-10 | Bayer Pharmaceuticals Corporation | Stabilized interleukin 2 |
MXPA02012272A (es) * | 2000-07-04 | 2003-04-25 | Novo Nordisk As | Compuestos heterociclicos que son inhibidores de la enzima dipeptidilpeptidasa-iv. |
WO2002014271A1 (fr) * | 2000-08-10 | 2002-02-21 | Mitsubishi Pharma Corporation | Dérivés de proline et leur utilisation comme médicaments |
US6821978B2 (en) | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
US20060034922A1 (en) | 2000-11-03 | 2006-02-16 | Andrx Labs, Llc | Controlled release metformin compositions |
US6722883B2 (en) | 2000-11-13 | 2004-04-20 | G & H Technologies Llc | Protective coating for abrasive dental tools and burs |
US6821261B2 (en) | 2000-12-12 | 2004-11-23 | Dj Orthopedics, Llc | Orthopedic brace having length-adjustable supports |
WO2002051836A1 (fr) | 2000-12-27 | 2002-07-04 | Kyowa Hakko Kogyo Co., Ltd. | Inhibiteur de dipeptidyl peptidase iv |
FR2818906B1 (fr) | 2000-12-29 | 2004-04-02 | Dospharma | Association medicamenteuse d'une biguanine et d'un transporteur, par exemple de metformine et d'arginine |
FR2819254B1 (fr) | 2001-01-08 | 2003-04-18 | Fournier Lab Sa | Nouveaux composes de la n-(phenylsulfonyl) glycine, leur procede de preparation et leur utilisation pour obtenir des compostions pharmaceutiques |
DE10117803A1 (de) | 2001-04-10 | 2002-10-24 | Boehringer Ingelheim Pharma | Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
DE10109021A1 (de) | 2001-02-24 | 2002-09-05 | Boehringer Ingelheim Pharma | Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
HUP0400058A2 (hu) | 2001-02-02 | 2004-04-28 | Takeda Chemical Industries, Ltd. | Kondenzált heterogyűrűs vegyületek, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk |
US6610326B2 (en) | 2001-02-16 | 2003-08-26 | Andrx Corporation | Divalproex sodium tablets |
US6649187B2 (en) | 2001-02-16 | 2003-11-18 | Bristol-Myers Squibb Pharma Company | Use of polyalkylamine polymers in controlled release devices |
DK1368349T3 (da) | 2001-02-24 | 2007-05-21 | Boehringer Ingelheim Pharma | Xanthinderivater, deres fremstilling og deres anvendelse som lægemidler |
US6936590B2 (en) | 2001-03-13 | 2005-08-30 | Bristol Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
US6693094B2 (en) | 2001-03-22 | 2004-02-17 | Chrono Rx Llc | Biguanide and sulfonylurea formulations for the prevention and treatment of insulin resistance and type 2 diabetes mellitus |
JP2002348279A (ja) | 2001-05-25 | 2002-12-04 | Nippon Kayaku Co Ltd | 光学活性ピリジルケトン誘導体の製造方法並びに光学活性ピリジルケトン誘導体 |
DE10130371A1 (de) | 2001-06-23 | 2003-01-02 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika, Corticosteroiden und Betamimetika |
GB0115517D0 (en) | 2001-06-25 | 2001-08-15 | Ferring Bv | Novel antidiabetic agents |
DE60235212D1 (de) | 2001-06-27 | 2010-03-11 | Smithkline Beecham Corp | Fluoropyrrolidine als Dipeptidylpeptidasehemmer |
DE60221983T2 (de) | 2001-06-27 | 2008-05-15 | Smithkline Beecham Corp. | Fluorpyrrolidine als dipeptidyl-peptidase inhibitoren |
EP1404675B1 (en) | 2001-07-03 | 2008-03-12 | Novo Nordisk A/S | Dpp-iv-inhibiting purine derivatives for the treatment of diabetes |
US6869947B2 (en) * | 2001-07-03 | 2005-03-22 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme DPP-IV |
UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
MXPA04000224A (es) | 2001-07-10 | 2005-07-25 | 4Sc Ag | Novedosos compuestos como agentes antiinflamatorios, inmunomoduladores y antiproliferativos. |
US7085258B2 (en) * | 2001-07-19 | 2006-08-01 | International Business Machines Corporation | Instant messaging with voice conversation feature |
US7638522B2 (en) | 2001-08-13 | 2009-12-29 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile |
AR035119A1 (es) | 2001-08-16 | 2004-04-14 | Lilly Co Eli | Anticuerpos humanos antagonistas anti-htnfsf13b |
CA2460512A1 (en) | 2001-09-14 | 2003-03-27 | Mitsubishi Pharma Corporation | Thiazolidine derivatives and medicinal use thereof |
WO2003024965A2 (en) | 2001-09-19 | 2003-03-27 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme dpp-iv |
CN1568166A (zh) | 2001-10-15 | 2005-01-19 | 荷姆泰克股份有限公司 | 预防再狭窄的涂层支架 |
DE10151296A1 (de) | 2001-10-17 | 2003-04-30 | Boehringer Ingelheim Pharma | Keratinozyten verwendbar als biologisch aktive Substanz bei der Behandlung von Wunden |
US6723340B2 (en) | 2001-10-25 | 2004-04-20 | Depomed, Inc. | Optimal polymer mixtures for gastric retentive tablets |
US20030083354A1 (en) | 2001-10-26 | 2003-05-01 | Pediamed Pharmaceuticals, Inc. | Phenylephrine tannate and pyrilamine tannate salts in pharmaceutical compositions |
US6861440B2 (en) | 2001-10-26 | 2005-03-01 | Hoffmann-La Roche Inc. | DPP IV inhibitors |
CA2363053C (en) | 2001-11-09 | 2011-01-25 | Bernard Charles Sherman | Clopidogrel bisulfate tablet formulation |
US20040171836A1 (en) | 2001-12-21 | 2004-09-02 | Toshihiro Fujino | Method for producing optical-active cis-piperidine derivatives |
US6727261B2 (en) | 2001-12-27 | 2004-04-27 | Hoffman-La Roche Inc. | Pyrido[2,1-A]Isoquinoline derivatives |
EP1466621A4 (en) | 2001-12-28 | 2009-05-27 | Nrl Pharma Inc | COMPOSITIONS FOR ENHANCING LIPID METABOLISM |
US20070197552A1 (en) | 2002-01-11 | 2007-08-23 | Novo Nordisk A/S | Method and composition for treatment of diabetes, hypertension, chronic heart failure and fluid retentive states |
EP1496877B1 (en) * | 2002-01-11 | 2008-10-01 | Novo Nordisk A/S | Method and composition for treatment of diabetes, hypertension, chronic heart failure and fluid retentive states |
RS52012B (en) | 2002-01-16 | 2012-04-30 | Boehringer Ingelheim Pharma Gmbh&Co.Kg. | TWO-TABLET PHARMACEUTICAL TABLE CONTAINING TELMISARTAN AND DIURETIC AND ITS PREPARATION |
EP1477182A4 (en) | 2002-01-21 | 2009-05-27 | Nrl Pharma Inc | NEW ANALGETICS |
EP1333033A1 (en) | 2002-01-30 | 2003-08-06 | Boehringer Ingelheim Pharma GmbH & Co.KG | FAP-activated anti-tumor compounds |
BR0307516A (pt) * | 2002-02-01 | 2004-12-07 | Pfizer Prod Inc | Formas de dosagem de liberação imediata contendo dispersões de uma droga sólida |
US7610153B2 (en) | 2002-02-13 | 2009-10-27 | Virginia Commonwealth University | Multi-drug titration and evaluation |
NZ535456A (en) | 2002-02-21 | 2006-08-31 | Biovail Lab Int Srl | Modified release formulations of at least one form of tramadol for oral administration |
EP1338595B1 (en) | 2002-02-25 | 2006-05-03 | Eisai Co., Ltd. | Xanthine derivatives as DPP-IV inhibitors |
HUP0200849A2 (hu) | 2002-03-06 | 2004-08-30 | Sanofi-Synthelabo | N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
JP4298212B2 (ja) | 2002-03-29 | 2009-07-15 | 大日本印刷株式会社 | 塩酸エピナスチン高融点型結晶の製造法 |
JP2003300977A (ja) | 2002-04-10 | 2003-10-21 | Sumitomo Pharmaceut Co Ltd | キサンチン誘導体 |
AU2003226051A1 (en) | 2002-04-16 | 2003-11-03 | Banyu Pharmaceutical Co., Ltd. | Solid forms of salts with tyrosine kinase activity |
CA2484306A1 (en) | 2002-04-26 | 2003-11-06 | Katsumi Maezono | Prophylactic and therapeutic agent of diabetes mellitus |
AU2003231252A1 (en) | 2002-05-09 | 2003-11-11 | Enos Pharmaceuticals, Inc. | Methods and compositions for the treatment and prevention of intermittent claudication or alzheimer's disease |
GB0212412D0 (en) | 2002-05-29 | 2002-07-10 | Novartis Ag | Combination of organic compounds |
ATE336494T1 (de) * | 2002-05-31 | 2006-09-15 | Schering Corp | Verfahren zur herstellung von xanthin phosphodiesterase v inhibitoren und deren vorstufen |
RU2297418C9 (ru) | 2002-06-06 | 2009-01-27 | Эйсай Ко., Лтд. | Новые конденсированные производные имидазола, ингибитор дипептидилпептидазы iv, фармацевтическая композиция, способ лечения и применение на их основе |
ES2199061B1 (es) * | 2002-06-10 | 2005-02-16 | Laboratorios Vita, S.A. | Comprimidos bucodispersables y procedimiento para su obtencion. |
FR2840897B1 (fr) | 2002-06-14 | 2004-09-10 | Fournier Lab Sa | Nouveaux derives d'arylsulfonamides et leur utilisation en therapeutique |
US20040002615A1 (en) | 2002-06-28 | 2004-01-01 | Allen David Robert | Preparation of chiral amino-nitriles |
US7065367B2 (en) * | 2002-07-11 | 2006-06-20 | Oliver Michaelis | Interface selection in a wireless communication network |
US20040023981A1 (en) | 2002-07-24 | 2004-02-05 | Yu Ren | Salt forms with tyrosine kinase activity |
AR040661A1 (es) | 2002-07-26 | 2005-04-13 | Theravance Inc | Diclorhidrato cristalino de n-{2-[-((r)-2-hidroxi-2-feniletilamino)fenil]etil}-(r)-2hidroxi-2-(3-formamido-4-hidroxifenil)etilamina, agonista del receptor adrenergico beta 2 |
TW200404796A (en) | 2002-08-19 | 2004-04-01 | Ono Pharmaceutical Co | Nitrogen-containing compound |
US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
DE10238243A1 (de) | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
US7495005B2 (en) * | 2002-08-22 | 2009-02-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, their preparation and their use in pharmaceutical compositions |
DE10238477A1 (de) | 2002-08-22 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Purinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
DE10238470A1 (de) | 2002-08-22 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
US7569574B2 (en) * | 2002-08-22 | 2009-08-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Purine derivatives, the preparation thereof and their use as pharmaceutical compositions |
DE10238724A1 (de) | 2002-08-23 | 2004-03-04 | Bayer Ag | Alkyl-substituierte Pyrazolpyrimidine |
DE10238723A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Phenyl-substituierte Pyrazolyprimidine |
JP2004123738A (ja) * | 2002-09-11 | 2004-04-22 | Takeda Chem Ind Ltd | 徐放性製剤 |
EP1545474A1 (en) * | 2002-09-16 | 2005-06-29 | Wyeth | Delayed release formulations for oral administration of a polypeptide therapeutic agent and methods of using same |
JPWO2004028524A1 (ja) | 2002-09-26 | 2006-01-19 | エーザイ株式会社 | 併用医薬 |
WO2004032905A1 (en) * | 2002-10-08 | 2004-04-22 | Ranbaxy Laboratories Limited | Gabapentin tablets and methods for their preparation |
WO2004033455A2 (en) | 2002-10-08 | 2004-04-22 | Novo Nordisk A/S | Hemisuccinate salts of heterocyclic dpp-iv inhibitors |
US20040122048A1 (en) | 2002-10-11 | 2004-06-24 | Wyeth Holdings Corporation | Stabilized pharmaceutical composition containing basic excipients |
US6861526B2 (en) | 2002-10-16 | 2005-03-01 | Pfizer Inc. | Process for the preparation of (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine |
PT1556362E (pt) | 2002-10-18 | 2008-06-16 | Merck & Co Inc | Compostos beta-amino heterocíclicos inibidores da dipeptidil peptidase para o tratamento ou prevenção da diabetes |
JP2004161749A (ja) | 2002-10-24 | 2004-06-10 | Toray Fine Chemicals Co Ltd | 光学活性含窒素化合物の製造方法 |
AU2003280680A1 (en) | 2002-11-01 | 2004-06-18 | Sumitomo Pharmaceuticals Co., Ltd. | Xanthine compound |
US7157490B2 (en) | 2002-11-07 | 2007-01-02 | Merck & Co., Inc. | Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
DE10251927A1 (de) | 2002-11-08 | 2004-05-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
US7482337B2 (en) * | 2002-11-08 | 2009-01-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions |
DE10254304A1 (de) | 2002-11-21 | 2004-06-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
US7109192B2 (en) * | 2002-12-03 | 2006-09-19 | Boehringer Ingelheim Pharma Gmbh & Co Kg | Substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions |
UY28103A1 (es) | 2002-12-03 | 2004-06-30 | Boehringer Ingelheim Pharma | Nuevas imidazo-piridinonas sustituidas, su preparación y su empleo como medicacmentos |
US20060111428A1 (en) | 2002-12-10 | 2006-05-25 | Pei-Ran Wang | Combination of an dpp-iv inhibitor and a ppar-alpha compound |
DE10351663A1 (de) | 2002-12-20 | 2004-07-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pulverförmige Arzneimittel enthaltend ein Tiotropiumsalz und Salmeterolxinafoat |
US20040152720A1 (en) | 2002-12-20 | 2004-08-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Powdered medicaments containing a tiotropium salt and salmeterol xinafoate |
PT1599222E (pt) | 2003-01-08 | 2009-06-12 | Novartis Vaccines & Diagnostic | Composições aquosas estabilizadas que contêm um inibidor da via do factor tecidular (tfpi) ou uma variante do inibidor da via do factor tecidular |
EP1599468B1 (en) | 2003-01-14 | 2007-10-03 | Arena Pharmaceuticals, Inc. | 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
DE10335027A1 (de) | 2003-07-31 | 2005-02-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von Angiotensin II Rezeptor Antagonisten |
PE20040950A1 (es) | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
JP2004250336A (ja) * | 2003-02-18 | 2004-09-09 | Kao Corp | コーティング錠及び糖衣錠の製造法 |
US7135575B2 (en) | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
US7442387B2 (en) | 2003-03-06 | 2008-10-28 | Astellas Pharma Inc. | Pharmaceutical composition for controlled release of active substances and manufacturing method thereof |
CA2515289A1 (en) | 2003-03-12 | 2004-09-23 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Weak base salts |
US20060159746A1 (en) | 2003-03-18 | 2006-07-20 | Troup John P | Compositions comprising fatty acids and amino acids |
PT2368553E (pt) | 2003-04-08 | 2015-03-03 | Progenics Pharm Inc | Formulações farmacêuticas contendo metilnaltrexona |
JPWO2004096806A1 (ja) | 2003-04-30 | 2006-07-13 | 大日本住友製薬株式会社 | 縮合イミダゾール誘導体 |
US20040220186A1 (en) | 2003-04-30 | 2004-11-04 | Pfizer Inc. | PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease |
TW200510277A (en) | 2003-05-27 | 2005-03-16 | Theravance Inc | Crystalline form of β2-adrenergic receptor agonist |
FR2855521B1 (fr) | 2003-05-28 | 2005-08-05 | Flamel Tech Sa | Polyaminoacides fonctionnalises par au moins un groupement h ydrophobe et leurs applications notamment therapeutiques. |
AU2003902828A0 (en) | 2003-06-05 | 2003-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Dpp-iv inhibitor |
DE10327439A1 (de) | 2003-06-18 | 2005-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazopyridazinon- und Imidazopyridonderivate, deren Herstellung und deren Verwendung als Arzneimittel |
US7566707B2 (en) * | 2003-06-18 | 2009-07-28 | Boehringer Ingelheim International Gmbh | Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions |
CA2529443C (en) | 2003-06-20 | 2012-06-05 | F. Hoffmann-La Roche Ag | Pyrido[2,1-a]-isoquinoline derivatives as dpp-iv inhibitors |
BRPI0411509A (pt) | 2003-06-20 | 2006-07-25 | Hoffmann La Roche | compostos, processo para a sua manufatura, composições farmacêuticas que compreendem os mesmos, método para tratamento e/ou profilaxia de enfermidades que estão associadas com dpp-iv e sua utilização |
JO2625B1 (en) * | 2003-06-24 | 2011-11-01 | ميرك شارب اند دوم كوربوريشن | Phosphoric acid salts of dipeptidyl betidase inhibitor 4 |
US7364755B2 (en) | 2003-07-07 | 2008-04-29 | Synthon Ip Inc. | Modified calcium phosphate excipient |
AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
NZ544200A (en) | 2003-07-14 | 2009-07-31 | Arena Pharm Inc | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
US20050027012A1 (en) | 2003-07-16 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Tablets containing ambroxol |
US20060134206A1 (en) | 2003-07-24 | 2006-06-22 | Iyer Eswaran K | Oral compositions for treatment of diseases |
JP2007501189A (ja) * | 2003-08-01 | 2007-01-25 | ジェネラブス テクノロジーズ,インコーポレイテッド | フラビウイルス科に対する二環式イミダゾール誘導体 |
US6995183B2 (en) | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
BRPI0413518A (pt) | 2003-08-14 | 2006-10-10 | Novo Nordisk Healthcare Ag | composição farmacêutica lìquida aquosa, método para preparar e uso da mesma, método para tratar uma sìndrome responsiva ao fator vii, e, recipiente hermético |
CN1964714B (zh) * | 2003-08-29 | 2011-09-28 | Hdac默克研究有限责任公司 | 辛二酰苯胺异羟肟酸和吉西他滨在制备用于治疗癌症的药物中的用途 |
JP2007505121A (ja) | 2003-09-08 | 2007-03-08 | 武田薬品工業株式会社 | ジペプチジルぺプチダーゼ阻害剤 |
US20070072810A1 (en) | 2003-10-03 | 2007-03-29 | Takeda Pharmaceutical Company, Limited | Agent for treating diabetes |
US7107714B2 (en) | 2003-11-10 | 2006-09-19 | Marketing Displays, Inc. | Portable snap-fit sign stand |
EP2839832A3 (en) | 2003-11-17 | 2015-06-24 | Novartis AG | Use of dipeptidyl peptidase IV inhibitors |
DE10355304A1 (de) * | 2003-11-27 | 2005-06-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
JPWO2005053695A1 (ja) * | 2003-12-04 | 2007-12-06 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 多発性硬化症予防剤または治療剤 |
US7217711B2 (en) * | 2003-12-17 | 2007-05-15 | Boehringer Ingelheim International Gmbh | Piperazin-1-yl and 2-([1,4]diazepan-1-yl)-imidazo[4,5-d]-pyridazin-4-ones, the preparation thereof and their use as pharmaceutical compositions |
DE10359098A1 (de) | 2003-12-17 | 2005-07-28 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 2-(Piperazin-1-yl)- und 2-([1,4]Diazepan-1-yl)-imidazo[4,5-d]pyridazin-4-one, deren Herstellung und deren Verwendung als Arzneimittel |
RU2381224C2 (ru) * | 2003-12-18 | 2010-02-10 | Тиботек Фармасьютикалз Лтд. | Пиперидинаминобензимидазольные производные как ингибиторы репликации респираторного синцитиального вируса |
DE10360835A1 (de) | 2003-12-23 | 2005-07-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Imidazolverbindungen, deren Herstellung und deren Verwendung als Arzneimittel |
US8207147B2 (en) | 2003-12-24 | 2012-06-26 | Prosidion Limited | Heterocyclic derivatives as GPCR receptor agonists |
EP1708680A2 (en) | 2004-01-21 | 2006-10-11 | Janssen Pharmaceutica N.V. | Mitratapide oral solution |
SE0400234D0 (sv) | 2004-02-06 | 2004-02-06 | Active Biotech Ab | New compounds, methods for their preparation and use thereof |
US7501426B2 (en) * | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
PL1758905T3 (pl) | 2004-02-18 | 2009-10-30 | Boehringer Ingelheim Int | 8-[3-Aminopiperydyn-1-ylo]-ksantyna, jej wytwarzanie i jej zastosowanie jako inhibitora DPP-IV |
DE102004019540A1 (de) | 2004-04-22 | 2005-11-10 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittelkombinationen zur Behandlung von Atemwegserkrankungen |
DE102004009039A1 (de) * | 2004-02-23 | 2005-09-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel |
EP1593671A1 (en) | 2004-03-05 | 2005-11-09 | Graffinity Pharmaceuticals AG | DPP-IV inhibitors |
US7393847B2 (en) * | 2004-03-13 | 2008-07-01 | Boehringer Ingleheim International Gmbh | Imidazopyridazinediones, their preparation and their use as pharmaceutical compositions |
AU2004318013B8 (en) | 2004-03-15 | 2011-10-06 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
SI1730131T1 (sl) | 2004-03-16 | 2012-08-31 | Boehringer Ingelheim Int | Glukopiranozil-substituirani benzenski derivati, zdravila, ki vsebujejo te spojine, njihova uporaba in postopek za njihovo pripravo |
EP1577306A1 (de) | 2004-03-17 | 2005-09-21 | Boehringer Ingelheim Pharma GmbH & Co.KG | Neue Benzoxazinonderivate als langwirksame Betamimetika zur Behandlung von Atemwegserkrankungen |
JP2007531780A (ja) | 2004-04-10 | 2007-11-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規な2−アミノ−イミダゾ[4,5−d]ピリダジン−4−オン及び2−アミノ−イミダゾ[4,5−c]ピリダジン−4−オン、その製法及び医薬としての使用 |
US7179809B2 (en) * | 2004-04-10 | 2007-02-20 | Boehringer Ingelheim International Gmbh | 2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions |
US20050239778A1 (en) | 2004-04-22 | 2005-10-27 | Boehringer Ingelheim International Gmbh | Novel medicament combinations for the treatment of respiratory diseases |
US20050244502A1 (en) | 2004-04-28 | 2005-11-03 | Mathias Neil R | Composition for enhancing absorption of a drug and method |
EP1744737A2 (en) | 2004-05-03 | 2007-01-24 | Omega Bio-Pharma (I.P.3) Limited | Cysteamines for treating complications of hypercholesterolemia and diabetes |
US7439370B2 (en) * | 2004-05-10 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides |
JP4227660B2 (ja) | 2004-05-12 | 2009-02-18 | ファイザー・プロダクツ・インク | ジペプチジルペプチダーゼivインヒビターとしてのプロリン誘導体およびそれらの使用 |
DE102004024454A1 (de) | 2004-05-14 | 2005-12-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Enantiomerenreine Betaagonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
PE20060315A1 (es) | 2004-05-24 | 2006-05-15 | Irm Llc | Compuestos de tiazol como moduladores de ppar |
TWI354569B (en) * | 2004-05-28 | 2011-12-21 | Bristol Myers Squibb Co | Coated tablet formulation and method |
BRPI0510527A (pt) | 2004-06-01 | 2007-10-30 | Ares Trading Sa | método de estabilização de proteìnas |
WO2005117861A1 (en) | 2004-06-04 | 2005-12-15 | Novartis Ag | Use of organic compounds |
EP1753459A2 (en) | 2004-06-09 | 2007-02-21 | Yasoo Health | Composition and method for improving pancreatic islet cell survival |
DE102004030502A1 (de) | 2004-06-24 | 2006-01-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel |
CA2511269A1 (en) | 2004-07-07 | 2006-01-07 | F. Hoffmann-La Roche Ag | Multimarker panel based on p1gf for diabetes type 1 and 2 |
BRPI0513384A (pt) | 2004-07-14 | 2008-05-06 | Novartis Ag | combinação de inibidores de dpp-iv e compostos que modulam receptores de 5-ht3 e/ou 5-ht4 |
JP2006045156A (ja) | 2004-08-06 | 2006-02-16 | Sumitomo Pharmaceut Co Ltd | 縮合ピラゾール誘導体 |
TW200613275A (en) | 2004-08-24 | 2006-05-01 | Recordati Ireland Ltd | Lercanidipine salts |
WO2006022428A1 (ja) | 2004-08-26 | 2006-03-02 | Takeda Pharmaceutical Company Limited | 糖尿病治療剤 |
DE102004043944A1 (de) * | 2004-09-11 | 2006-03-30 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 8-(3-Amino-piperidin-1-yl)-7-(but-2-inyl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
DE102004044221A1 (de) | 2004-09-14 | 2006-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 3-Methyl-7-butinyl-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
CN1759834B (zh) | 2004-09-17 | 2010-06-23 | 中国医学科学院医药生物技术研究所 | 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途 |
EP1799637A1 (en) | 2004-09-23 | 2007-06-27 | Amgen, Inc | Substituted sulfonamidopropionamides and methods of use |
CA2580266A1 (en) | 2004-10-08 | 2006-04-20 | Novartis Ag | Combination of organic compounds |
EP1799639B1 (en) | 2004-10-12 | 2013-09-04 | Glenmark Pharmaceuticals S.A. | Novel dipeptidyl peptidase iv inhibitors, pharmaceutical compositions containing them, and process for their preparation |
US20090253752A1 (en) | 2004-10-25 | 2009-10-08 | Bryan Burkey | Combination of dpp-iv inhibitor, ppar antidiabetic and metmorfin |
DE102005013967A1 (de) | 2004-11-05 | 2006-10-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Bradykinin-B1-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel |
DE102004054054A1 (de) * | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
JP2006137678A (ja) | 2004-11-10 | 2006-06-01 | Shionogi & Co Ltd | インターロイキン−2組成物 |
RU2382786C2 (ru) | 2004-12-24 | 2010-02-27 | ДАЙНИППОН СУМИТОМО ФАРМА Ко., ЛТД. | Бициклические производные пиррола |
KR100760430B1 (ko) | 2004-12-31 | 2007-10-04 | 한미약품 주식회사 | 당뇨병 치료제의 경구 투여용 서방성 복합 제제 및 이의제조 방법 |
DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
GT200600008A (es) | 2005-01-18 | 2006-08-09 | Formulacion de compresion directa y proceso | |
EP1874339A1 (en) | 2005-04-21 | 2008-01-09 | Gastrotech Pharma A/S | Pharmaceutical preparations of a glp-1 molecule and an anti-emetic drug |
ZA200708179B (en) | 2005-04-22 | 2009-12-30 | Alantos Pharmaceuticals Holding Inc | Dipeptidyl peptidase-IV inhibitors |
UA91546C2 (uk) | 2005-05-03 | 2010-08-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ |
CA2609186A1 (en) | 2005-05-25 | 2006-11-30 | Wyeth | Methods of synthesizing substituted 3-cyanoquinolines and intermediates thereof |
EP1894567B1 (en) | 2005-06-03 | 2012-08-15 | Mitsubishi Tanabe Pharma Corporation | Concomitant pharmaceutical agents and use thereof |
GT200600218A (es) | 2005-06-10 | 2007-03-28 | Formulación y proceso de compresión directa | |
KR101374304B1 (ko) | 2005-06-20 | 2014-03-14 | 디코드 제네틱스 이에이치에프 | 타입 2 당뇨병의 위험에 대한 진단 마커인 tcf7l2유전자의 유전적 변이체 |
CA2614314A1 (en) | 2005-07-08 | 2007-01-18 | Pfizer Limited | Human anti-madcam antibodies |
UY29694A1 (es) | 2005-07-28 | 2007-02-28 | Boehringer Ingelheim Int | Metodos para prevenir y tratar trastornos metabolicos y nuevos derivados de pirazol-o-glucosido |
DE102005035891A1 (de) * | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
WO2007017423A2 (en) * | 2005-08-11 | 2007-02-15 | F. Hoffmann-La Roche Ag | Pharmaceutical composition comprising a dpp-iv inhibitor |
EP1760076A1 (en) | 2005-09-02 | 2007-03-07 | Ferring B.V. | FAP Inhibitors |
CA2622608C (en) | 2005-09-14 | 2014-08-19 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors for treating diabetes |
WO2007033350A1 (en) | 2005-09-14 | 2007-03-22 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors for treating diabetes |
CN101263135A (zh) | 2005-09-16 | 2008-09-10 | 艾尼纳制药公司 | 代谢调节剂和代谢相关病症的治疗 |
AU2006292377B2 (en) | 2005-09-20 | 2011-03-03 | Emisphere Technologies, Inc. | Use of a DPP-IV inhibitor to reduce hypoglycemic events |
EP1945190A1 (en) | 2005-09-22 | 2008-07-23 | Swissco Devcelopment AG | Effervescent metformin composition and tablets and granules made therefrom |
JOP20180109A1 (ar) | 2005-09-29 | 2019-01-30 | Novartis Ag | تركيبة جديدة |
BRPI0616640A2 (pt) | 2005-09-30 | 2011-06-28 | Novartis Ag | combinação de compostos orgánicos |
CA2625646A1 (en) | 2005-10-25 | 2007-05-03 | Merck & Co., Inc. | Combination of a dipeptidyl peptidase-4 inhibitor and an anti-hypertensive agent for the treatment of diabetes and hypertension |
CN101300298A (zh) | 2005-11-04 | 2008-11-05 | Ls电线有限公司 | Mdh-聚合物混合粒子的合成 |
JP5165582B2 (ja) | 2005-12-16 | 2013-03-21 | メルク・シャープ・エンド・ドーム・コーポレイション | ジペプチジルペプチダーゼ−4インヒビターとメトホルミンとを組み合わせた医薬組成物 |
BRPI0620643A2 (pt) | 2005-12-23 | 2011-12-20 | Novartis Ag | compostos de heterocìclicos condensados úteis como inibidores de dpp-iv, formulações farmacêuticas, produtos e usos dos compostos |
GB0526291D0 (en) | 2005-12-23 | 2006-02-01 | Prosidion Ltd | Therapeutic method |
US20090054512A1 (en) | 2006-01-06 | 2009-02-26 | Foley James E | Use of organic compounds |
TW200801029A (en) | 2006-02-15 | 2008-01-01 | Boehringer Ingelheim Int | Glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their use and process for their manufacture |
WO2007099345A1 (en) | 2006-03-02 | 2007-09-07 | Betagenon Ab | Medical use of bmp-2 and/ or bmp-4 |
PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
US8455435B2 (en) | 2006-04-19 | 2013-06-04 | Ludwig-Maximilians-Universitat Munchen | Remedies for ischemia |
EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
MX2008014024A (es) | 2006-05-04 | 2008-11-14 | Boehringer Ingelheim Int | Formas poliformas. |
KR20070111099A (ko) | 2006-05-16 | 2007-11-21 | 영진약품공업주식회사 | 시타글립틴 염산염의 신규 결정형, 이의 제조 방법과 이를포함하는 약학적 조성물 |
AU2007254309B2 (en) | 2006-05-16 | 2012-05-03 | Gilead Sciences, Inc. | Method and compositions for treating hematological malignancies |
US20080064717A1 (en) | 2006-05-19 | 2008-03-13 | Rajesh Iyengar | Inhibitors of diacylglycerol O-acyltransferase type 1 enzyme |
KR100858848B1 (ko) | 2006-05-23 | 2008-09-17 | 한올제약주식회사 | 메트포르민 서방정 |
WO2007149797A2 (en) | 2006-06-19 | 2007-12-27 | Novartis Ag | Use of organic compounds |
WO2007148185A2 (en) | 2006-06-21 | 2007-12-27 | Pfizer Products Inc. | Substituted 3 -amino- pyrrolidino-4 -lactams as dpp inhibitors |
AT503443B1 (de) | 2006-06-23 | 2007-10-15 | Leopold Franzens Uni Innsbruck | Verfahren zur herstellung einer eisfläche für eissportbahnen |
TW200811140A (en) | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
TW200811147A (en) | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
JP2010500326A (ja) | 2006-08-08 | 2010-01-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 糖尿病の治療のためのdpp−iv阻害剤としてのピロロ[3,2−d]ピリミジン |
EP2054426A1 (en) | 2006-08-15 | 2009-05-06 | Boehringer Ingelheim International GmbH | Glucopyranosyl-substituted cyclopropylbenzene derivatives, pharmaceutical compositions containing such compounds, their use as sglt inhibitors and process for their manufacture |
NZ574664A (en) | 2006-08-17 | 2012-06-29 | Wellstat Therapeutics Corp | Combination treatment for metabolic disorders comprising an incretin mimetic such as exendin or a dppv iv inhibitor |
DE102006042586B4 (de) | 2006-09-11 | 2014-01-16 | Betanie B.V. International Trading | Verfahren zum mikropartikulären Beladen von hochpolymeren Kohlenhydraten mit hydrophoben Wirkflüssigkeiten |
AR063569A1 (es) | 2006-11-06 | 2009-02-04 | Boehringer Ingelheim Int | Derivados de benzil- benzonitrilo sustituidos con glucopiranosilo medicamentos que contienen a compuestos de este tipo su uso u procedimiento para su fabricacion |
US7956201B2 (en) | 2006-11-06 | 2011-06-07 | Hoffman-La Roche Inc. | Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one |
US20100298243A1 (en) | 2006-11-09 | 2010-11-25 | Boehringer Ingelheim International Gmbh | Combination therapy with sglt-2 inhibitors and their pharmaceutical compositions |
WO2008070692A2 (en) | 2006-12-06 | 2008-06-12 | Smithkline Beecham Corporation | Bicyclic compounds and use as antidiabetics |
ES2319596B1 (es) | 2006-12-22 | 2010-02-08 | Laboratorios Almirall S.A. | Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico. |
US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
CL2008000017A1 (es) | 2007-01-04 | 2008-08-01 | Prosidion Ltd | Compuestos derivados de heterociclos de nitrogeno y oxigeno, agonistas de gpcr; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento de la obesidad, diabetes, sindrome metabolico, hiperlipidemia, toleranci |
CL2008000133A1 (es) | 2007-01-19 | 2008-05-23 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un compuesto derivado de pirazol-o-glucosido combinado con al menos un segundo agente terapeutico; y uso de la composicion para el tratamiento de diabetes mellitus, cataratas, neuropatia, infarto de miocardio, e |
TW200836774A (en) | 2007-02-01 | 2008-09-16 | Takeda Pharmaceutical | Solid preparation |
MY147596A (en) | 2007-02-01 | 2012-12-31 | Takeda Pharmaceutical | Solid preparation comprising alogliptin and pioglitazone |
CA2677457A1 (en) | 2007-02-06 | 2008-08-14 | Helen Tuvesson Andersson | New compounds, methods for their preparation and use thereof |
EP2139464A1 (en) | 2007-03-15 | 2010-01-06 | Nectid, Inc. | Anti-diabetic combinations comprising a slow release biguanide composition and an immediate release dipeptidyl peptidase iv inhibitor composition |
JP5616630B2 (ja) | 2007-04-03 | 2014-10-29 | 田辺三菱製薬株式会社 | ジペプチジルペプチダーゼ4阻害化合物と甘味料との併用 |
AU2008242981B2 (en) | 2007-04-16 | 2014-06-12 | Smith & Nephew, Inc. | Powered surgical system |
PE20090696A1 (es) | 2007-04-20 | 2009-06-20 | Bristol Myers Squibb Co | Formas cristalinas de saxagliptina y procesos para preparar las mismas |
EP2144902B1 (en) | 2007-05-04 | 2012-05-16 | Bristol-Myers Squibb Company | [6,6]and [6,7]-bicyclic gpr119 g protein-coupled receptor agonists |
ES2398478T5 (es) | 2007-07-09 | 2016-02-25 | Symrise Ag | Sales solubles estables de ácido fenilbencimidazolsulfónico de pH 6,0 a menos de 6,8 |
KR101536786B1 (ko) | 2007-07-19 | 2015-07-14 | 다케다 야쿠힌 고교 가부시키가이샤 | 알로그립틴 및 메트포르민 히드로클로라이드를 포함하는 고체 제제 |
PE20090597A1 (es) | 2007-08-16 | 2009-06-06 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un derivado de pirazol-o-glucosido |
PE20090938A1 (es) | 2007-08-16 | 2009-08-08 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un derivado de benceno sustituido con glucopiranosilo |
CL2008002425A1 (es) | 2007-08-16 | 2009-09-11 | Boehringer Ingelheim Int | Composición farmacéutica que comprende un inhibidor de sglt2 y 1-(4-metil-quinazolin-2-il)metil-3metil-7-(-2-butin-1-il)-8-(3-(r)-amino-piperidin-1il)-xantina, un inhibidor de dpp iv y su uso para el tratamiento de la obesidad y de la diabetes tipo 1 y 2 y complicaciones de esta. |
CL2008002424A1 (es) | 2007-08-16 | 2009-09-11 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un compuesto derivado de pirazol-o-glucosido; y uso de la composicion farmaceutica para el tratamiento de la diabetes mellitus, tolerancia anormal a la glucosa e hiperglucemia, trastornos metabolicos, entre otras. |
AU2008290582B2 (en) | 2007-08-17 | 2014-08-14 | Boehringer Ingelheim International Gmbh | Purin derivatives for use in the treatment of fab-related diseases |
GB2465132B (en) | 2007-09-21 | 2012-06-06 | Lupin Ltd | Compounds as dipeptidyl peptidase IV (DPP IV) inhibitors |
BRPI0820535B8 (pt) | 2007-11-16 | 2021-05-25 | Novo Nordisk As | composições farmacêuticas contendo insulina e um peptídeo insulinotrópico |
CN101234105A (zh) | 2008-01-09 | 2008-08-06 | 北京润德康医药技术有限公司 | 一种含有二甲双胍和维格列汀的药用组合物及其制备方法 |
US20090186086A1 (en) | 2008-01-17 | 2009-07-23 | Par Pharmaceutical, Inc. | Solid multilayer oral dosage forms |
CL2008003653A1 (es) | 2008-01-17 | 2010-03-05 | Mitsubishi Tanabe Pharma Corp | Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica. |
TW200936136A (en) | 2008-01-28 | 2009-09-01 | Sanofi Aventis | Tetrahydroquinoxaline urea derivatives, their preparation and their therapeutic application |
JP2011510986A (ja) | 2008-02-05 | 2011-04-07 | メルク・シャープ・エンド・ドーム・コーポレイション | メトホルミン及びジペプチジルペプチダーゼ−iv阻害剤の併用医薬組成物 |
EP2259676A4 (en) | 2008-03-04 | 2011-03-16 | Merck Sharp & Dohme | PHARMACEUTICAL COMPOSITIONS OF A COMBINATION OF METFORMIN AND A DIPEPTIDYL PEPTIDASE-IV INHIBITOR |
GEP20135844B (en) | 2008-03-05 | 2013-06-10 | Takeda Pharmaceutical | Heterocyclic compound |
US8551524B2 (en) | 2008-03-14 | 2013-10-08 | Iycus, Llc | Anti-diabetic combinations |
CA2719507C (en) | 2008-03-31 | 2018-03-27 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
PE20140960A1 (es) | 2008-04-03 | 2014-08-15 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
CN101590007A (zh) | 2008-05-27 | 2009-12-02 | 北京瑞伊人科技发展有限公司 | 一种盐酸二甲双胍/伏格列波糖降糖口服制剂组合物及其制备 |
PE20100156A1 (es) | 2008-06-03 | 2010-02-23 | Boehringer Ingelheim Int | Tratamiento de nafld |
UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
KR20200118243A (ko) | 2008-08-06 | 2020-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
JP2010053576A (ja) | 2008-08-27 | 2010-03-11 | Sumitomo Forestry Co Ltd | 舗装用マット |
WO2010029089A2 (en) | 2008-09-10 | 2010-03-18 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
UY32177A (es) | 2008-10-16 | 2010-05-31 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con control glucémico insuficiente a pesar de la terapia con fármaco, oral o no, antidiabético |
WO2010045656A2 (en) | 2008-10-17 | 2010-04-22 | Nectid, Inc. | Novel sglt2 inhibitor dosage forms |
WO2010072776A1 (en) | 2008-12-23 | 2010-07-01 | Boehringer Ingelheim International Gmbh | Salt forms of organic compound |
AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
UY32048A (es) | 2009-01-08 | 2010-03-26 | Boehringer Ingelheim Int | Derivados sustituido de 1-(sustituido)-3-metil-7-(sustituido)-8-(3-(R)-amino-piperidin-1-il)cantina y derivados sustituidos de 1-(sustituido) - 4 - fluoropirrolidin- 2 - carbonitrilo y sus sales famacéuticamente aceptables como inhibidores de DPP-4 y aplicaciones. |
TWI466672B (zh) | 2009-01-29 | 2015-01-01 | Boehringer Ingelheim Int | 小兒科病人糖尿病之治療 |
NZ619520A (en) | 2009-02-13 | 2015-06-26 | Boehringer Ingelheim Int | Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics |
UY32427A (es) | 2009-02-13 | 2010-09-30 | Boheringer Ingelheim Internat Gmbh | Composicion farmaceutica, forma farmaceutica, procedimiento para su preparacion, metodos de tratamiento y usos de la misma |
UA102429C2 (ru) | 2009-02-13 | 2013-07-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | Фармацевтическая композиция, которая включает ингибитор sglt-2, ингибитор дпп-iv и другой антидиабетический агент, и ее применение |
TW201031661A (en) | 2009-02-17 | 2010-09-01 | Targacept Inc | Fused benzazepines as neuronal nicotinic acetylcholine receptor ligands |
WO2010106457A2 (en) | 2009-03-20 | 2010-09-23 | Pfizer Inc. | 3-oxa-7-azabicyclo[3.3.1]nonanes |
US8815292B2 (en) | 2009-04-27 | 2014-08-26 | Revalesio Corporation | Compositions and methods for treating insulin resistance and diabetes mellitus |
AU2010241736B2 (en) | 2009-04-27 | 2016-01-28 | Revalesio Corporation | Compositions and methods for treating insulin resistance and diabetes mellitus |
WO2010140111A1 (en) | 2009-06-02 | 2010-12-09 | Ranbaxy Laboratories Limited | Pharmaceutical compositions containing a combination of an antihistamine and a decongestant |
EP2442806A1 (en) | 2009-06-15 | 2012-04-25 | Merck Sharp & Dohme Corp. | Pharmaceutical compositions of combinations of dipeptidyl peptidase-4 inhibitors with pioglitazone |
EP2456426A1 (en) | 2009-07-21 | 2012-05-30 | Keryx Biopharmaceuticals, Inc. | Ferric citrate dosage forms |
UY32919A (es) | 2009-10-02 | 2011-04-29 | Boehringer Ingelheim Int | Composición farmacéutica, forma de dosificación farmacéutica, procedimiento para su preparación, mé todos para su tratamiento y sus usos |
WO2011039367A2 (en) | 2009-10-02 | 2011-04-07 | Boehringer Ingelheim International Gmbh | Therapeutic uses of pharmaceutical compositions |
JP5446716B2 (ja) | 2009-10-21 | 2014-03-19 | 大正製薬株式会社 | アルギニン及びカルニチン含有錠剤の製造方法 |
CN102753161A (zh) | 2009-11-27 | 2012-10-24 | 贝林格尔.英格海姆国际有限公司 | 基因型糖尿病患者利用dpp-iv抑制剂例如利拉利汀的治疗 |
JP2010070576A (ja) | 2009-12-28 | 2010-04-02 | Sato Pharmaceutical Co Ltd | 速溶解性錠剤 |
TWI562775B (en) | 2010-03-02 | 2016-12-21 | Lexicon Pharmaceuticals Inc | Methods of using inhibitors of sodium-glucose cotransporters 1 and 2 |
WO2011113947A1 (en) | 2010-03-18 | 2011-09-22 | Boehringer Ingelheim International Gmbh | Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions |
ES2935300T3 (es) | 2010-05-05 | 2023-03-03 | Boehringer Ingelheim Int | Combiterapia |
MX2012012438A (es) | 2010-05-05 | 2012-11-29 | Boehringer Ingelheim Int | Formulaciones farmaceuticas que comprenden pioglitazona y linagliptina. |
ES2577930T3 (es) | 2010-06-09 | 2016-07-19 | Poxel | Derivados de triazina para retrasar el inicio de la diabetes tipo 1 |
CA2802335A1 (en) | 2010-06-22 | 2011-12-29 | Twi Pharmaceuticals, Inc. | Controlled release compositions with reduced food effect |
CN106975074A (zh) | 2010-06-24 | 2017-07-25 | 勃林格殷格翰国际有限公司 | 糖尿病治疗 |
WO2012031124A2 (en) | 2010-09-03 | 2012-03-08 | Bristol-Myers Squibb Company | Drug formulations using water soluble antioxidants |
WO2012039420A1 (ja) | 2010-09-21 | 2012-03-29 | 国立大学法人九州大学 | 動脈圧反射機能障害に関連した疾患を治療するためのバイオニック動脈圧反射システム |
US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
WO2012088682A1 (en) | 2010-12-29 | 2012-07-05 | Shanghai Fochon Pharmaceutical Co Ltd. | 2-(3-aminopiperidin-1-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-5,7(3h,6h)-dione derivates as dipeptidyl peptidase iv(dpp-iv) inhibitors |
WO2012106303A1 (en) | 2011-02-01 | 2012-08-09 | Bristol-Myers Squibb Company | Pharmaceutical formulations including an amine compound |
UY33937A (es) | 2011-03-07 | 2012-09-28 | Boehringer Ingelheim Int | Composiciones farmacéuticas que contienen inhibidores de dpp-4 y/o sglt-2 y metformina |
EP2707368B1 (en) | 2011-05-10 | 2016-02-03 | Sandoz AG | Polymorph of linagliptin benzoate |
WO2013010964A1 (en) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions |
US20130172244A1 (en) | 2011-12-29 | 2013-07-04 | Thomas Klein | Subcutaneous therapeutic use of dpp-4 inhibitor |
MX342355B (es) | 2012-01-04 | 2016-09-23 | Procter & Gamble | Estructuras fibrosas que contienen activos con multiples regiones. |
US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
WO2013171167A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
JP6374862B2 (ja) | 2012-05-24 | 2018-08-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 自己免疫性糖尿病、特に、ladaの治療に使用するためのdpp−4阻害剤としてのキサンチン誘導体 |
EP2854824A1 (en) | 2012-05-25 | 2015-04-08 | Boehringer Ingelheim International GmbH | Use of keratinocytes as a biologically active substance in the treatment of wounds, such as diabetic wounds, optionally in combination with a dpp-4 inhibitor |
WO2013179307A2 (en) | 2012-05-29 | 2013-12-05 | Mylan Laboratories Limited | Stabilized pharmaceutical compositions of saxagliptin |
MX2015002432A (es) | 2012-08-24 | 2015-06-22 | Novartis Ag | Inhibidores de la nep para el tratamiento de enfermedades caracterizadas por el ensanchamiento o remodelacion auricular. |
US20140100236A1 (en) | 2012-10-09 | 2014-04-10 | Boehringer Ingelheim International Gmbh | Use of selectively moisture-adjusted tabletting material in the production of mechanically stable tablets which contain at least one hydrate-forming active substance and/or adjuvant relevant to the mechanical stability of the tablets, particularly arginine-containing tablets |
JP2015533133A (ja) | 2012-10-09 | 2015-11-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 錠剤製造における水分調節崩壊剤の使用 |
US9050302B2 (en) | 2013-03-01 | 2015-06-09 | Jazz Pharmaceuticals Ireland Limited | Method of administration of gamma hydroxybutyrate with monocarboxylate transporters |
CA2903577C (en) | 2013-03-15 | 2023-10-17 | Boehringer Ingelheim International Gmbh | Use of linagliptin in cardio- and renoprotective antidiabetic therapy |
HRP20220365T1 (hr) | 2013-04-18 | 2022-05-13 | Boehringer Ingelheim International Gmbh | Farmaceutski pripravak, postupci za liječenje i njegove uporabe |
US20140343014A1 (en) | 2013-05-17 | 2014-11-20 | Boehringer Ingelheim International Gmbh | Combination of a certain dpp-4 inhibitor and voglibose |
WO2014198906A1 (en) | 2013-06-14 | 2014-12-18 | Boehringer Ingelheim International Gmbh | Dpp-4 inhibitors for treating diabetes and its complications |
US9526728B2 (en) | 2014-02-28 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Medical use of a DPP-4 inhibitor |
CN104130258B (zh) | 2014-08-13 | 2016-06-01 | 广东东阳光药业有限公司 | 一种二聚体的转化方法 |
WO2016059219A1 (en) | 2014-10-17 | 2016-04-21 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
BR112018072401A2 (pt) | 2016-06-10 | 2019-02-19 | Boehringer Ingelheim International Gmbh | combinações de linagliptina e metformina |
-
2006
- 2006-05-04 EP EP06009201A patent/EP1852108A1/en not_active Withdrawn
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6548481B1 (en) * | 1998-05-28 | 2003-04-15 | Probiodrug Ag | Effectors of dipeptidyl peptidase IV |
WO2004018468A2 (de) * | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-amino-piperidin-1-yl]-xanthine, deren herstellung und deren verwendung als arzneimittel |
EP1537880A1 (en) * | 2002-09-11 | 2005-06-08 | Takeda Pharmaceutical Company Limited | Sustained release preparation |
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